Journal of Biological Chemistry
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How Synapses Reuse and Recycle{diamondsuit}: A Distributed Set of Interactions Controls {micro}2 Functionality in the Role of AP-2 as a Sorting Adaptor in Synaptic Vesicle Endocytosis [Papers Of The Week]
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(Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Tags: Papers Of The Week Source Type: journals
TCR Goes Branching Out{diamondsuit}: T Cell Receptor Signaling Co-regulates Multiple Golgi Genes to Enhance N-Glycan Branching [Papers Of The Week]Email this article to a colleague.
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(Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Tags: Papers Of The Week Source Type: journals
Mixed Lineage Kinase Phosphorylates Transcription Factor E47 and Inhibits TrkB Expression to Link Neuronal Death and Survival Pathways [Mechanisms Of Signal Transduction]Email this article to a colleague.
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E47 is a basic helix-loop-helix transcription factor involved in neuronal differentiation and survival. We had previously shown that the basic helix-loop-helix protein E47 binds to E-box sequences within the promoter of the TrkB gene and activates its transcription. Proper expression of the TrkB receptor plays a key role in development and function of the vertebrate nervous system, and altered levels of TrkB have been associated with important human diseases. Here we show that E47 interacts with MLK2, a mixed lineage kinase (MLK) involved in JNK-mediated activation of programmed cell death. MLK2 enhances phosphorylation of...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Pedraza, N., Rafel, M., Navarro, I., Encinas, M., Aldea, M., Gallego, C. Tags: Mechanisms Of Signal Transduction Source Type: journals
Complex Regulation of Tartrate-resistant Acid Phosphatase (TRAP) Expression by Interleukin 4 (IL-4): IL-4 INDIRECTLY SUPPRESSES RECEPTOR ACTIVATOR OF NF-{kappa}B LIGAND (RANKL)-MEDIATED TRAP EXPRESSION BUT MODESTLY INDUCES ITS EXPRESSION DIRECTLY [Mechanisms Of Signal Transduction]Email this article to a colleague.
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Interleukin 4 (IL-4) inhibits receptor activator of NF-B ligand (RANKL)-induced osteoclast formation and functional activity in a STAT6-dependent manner. IL-4 down-regulates expression of tartrate-resistant acid phosphatase (TRAP) in mature osteoclasts. To determine whether IL-4 regulates TRAP promoter activity, RAW264.7 cells were transfected with a TRAP promoter-luciferase reporter. Treatment with IL-4 alone modestly enhanced TRAP luciferase activity. However, IL-4 suppressed the ability of RANKL to up-regulate TRAP-luciferase activity, suggesting that IL-4 has multiple effects on TRAP transcription. IL-4 also reduced th...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Yu, M., Moreno, J. L., Stains, J. P., Keegan, A. D. Tags: Mechanisms Of Signal Transduction Source Type: journals
ScFv Antibody-induced Translocation of Cell-surface Heparan Sulfate Proteoglycan to Endocytic Vesicles: EVIDENCE FOR HEPARAN SULFATE EPITOPE SPECIFICITY AND ROLE OF BOTH SYNDECAN AND GLYPICAN [Glycobiology and Extracellular Matrices]Email this article to a colleague.
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Cellular uptake of several viruses and polybasic macromolecules requires the expression of cell-surface heparan sulfate proteoglycan (HSPG) through as yet ill defined mechanisms. We unexpectedly found that among several cell-surface-binding single chain variable fragment (scFv) anti-HS antibody (HS) clones, only one, AO4B08, efficiently translocated macromolecular cargo to intracellular vesicles through induction of HSPG endocytosis. Interestingly, AO4B08-induced PG internalization was strictly dependent on HS 2-O-sulfation and appeared independent of intact N-sulfation. AO4B08 and human immunodeficiency virus (HIV)-Tat, i...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Wittrup, A., Zhang, S.-H., ten Dam, G. B., van Kuppevelt, T. H., Bengtson, P., Johansson, M., Welch, J., Morgelin, M., Belting, M. Tags: Glycobiology and Extracellular Matrices Source Type: journals
Interleukin-10 Facilitates Both Cholesterol Uptake and Efflux in Macrophages [Lipids and Lipoproteins: Metabolism, Regulation, and Signaling]Email this article to a colleague.
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We report here that a cytokine considered to be anti-atherogenic, interleukin-10 (IL10), promotes cholesterol uptake from modified lipoproteins in macrophages and its transformation into foam cells by increasing the expression of scavenger receptor CD36 and scavenger receptor A. Although uptake of modified lipoproteins is considered proatherogenic, we found that IL10 also increases cholesterol efflux from macrophages to protect against toxicity of free cholesterol accumulation in the cell. This process was PPAR-dependent and was mediated through up-regulation of ABCA1 (ATP-binding cassette transporter A1) protein expressio...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Han, X., Kitamoto, S., Lian, Q., Boisvert, W. A. Tags: Lipids and Lipoproteins: Metabolism, Regulation, and Signaling Source Type: journals
Naturally Occurring Mutations Alter the Stability of Polycystin-1 Polycystic Kidney Disease (PKD) Domains [Protein Structure and Folding]Email this article to a colleague.
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Mutations in polycystin-1 (PC1) can cause autosomal dominant polycystic kidney disease, which is a leading cause of renal failure. The available evidence suggests that PC1 acts as a mechanosensor, receiving signals from the primary cilia, neighboring cells, and extracellular matrix. PC1 is a large membrane protein that has a long N-terminal extracellular region (about 3000 amino acids) with a multimodular structure including 16 Ig-like polycystic kidney disease (PKD) domains, which are targeted by many naturally occurring missense mutations. Nothing is known about the effects of these mutations on the biophysical propertie...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Ma, L., Xu, M., Forman, J. R., Clarke, J., Oberhauser, A. F. Tags: Protein Structure and Folding Source Type: journals
Structure and Interdomain Dynamics of Apoptosis-associated Speck-like Protein Containing a CARD (ASC) [Protein Structure and Folding]Email this article to a colleague.
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This study reports the solution structure and interdomain dynamics of full-length ASC. The pyrin and CARD domains are structurally independent six-helix bundle motifs connected by a 23-residue linker. The CARD structure reveals two distinctive characteristics; helix 1 is not fragmented as in all other known CARDs, and its electrostatic surface shows a uniform distribution of positive and negative charges, whereas these are commonly separated into two areas in other death domains. The linker adopts residual structure resulting in a back-to-back orientation of the domains, which avoids steric interference of each domain with...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: de Alba, E. Tags: Protein Structure and Folding Source Type: journals
SAGA and Rpd3 Chromatin Modification Complexes Dynamically Regulate Heat Shock Gene Structure and Expression [Transcription, Chromatin, and Epigenetics]Email this article to a colleague.
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The chromatin structure of heat shock protein (HSP)-encoding genes undergoes dramatic alterations upon transcriptional induction, including, in extreme cases, domain-wide nucleosome disassembly. Here, we use a combination of gene knock-out, in situ mutagenesis, chromatin immunoprecipitation, and expression assays to investigate the role of histone modification complexes in regulating heat shock gene structure and expression in Saccharomyces cerevisiae. Two histone acetyltransferases, Gcn5 and Esa1, were found to stimulate HSP gene transcription. A detailed chromatin immunoprecipitation analysis of the Gcn5-containing SAGA ...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Kremer, S. B., Gross, D. S. Tags: Transcription, Chromatin, and Epigenetics Source Type: journals
Electrophilic Affibodies Forming Covalent Bonds to Protein Targets [Protein Structure and Folding]Email this article to a colleague.
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Antibody affinity limits sensitivity of detection in many areas of biology and medicine. High affinity usually depends on achieving the optimal combination of the natural 20 amino acids in the antibody binding site. Here, we investigate the effect on recognition of protein targets of placing an unnatural electrophile adjacent to the target binding site. We positioned a weak electrophile, acrylamide, near the binding site between an affibody, a non-immunoglobulin binding scaffold, and its protein target. The proximity between cysteine, lysine, or histidine on the target protein drove covalent bond formation to the electroph...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Holm, L., Moody, P., Howarth, M. Tags: Protein Structure and Folding Source Type: journals
Isolation and Characterization of Patient-derived, Toxic, High Mass Amyloid {beta}-Protein (A{beta}) Assembly from Alzheimer Disease Brains [Protein Structure and Folding]Email this article to a colleague.
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Amyloid β-protein (Aβ) assemblies are thought to play primary roles in Alzheimer disease (AD). They are considered to acquire surface tertiary structures, not present in physiologic monomers, that are responsible for exerting toxicity, probably through abnormal interactions with their target(s). Therefore, Aβ assemblies having distinct surface tertiary structures should cause neurotoxicity through distinct mechanisms. Aiming to clarify the molecular basis of neuronal loss, which is a central phenotype in neurodegenerative diseases such as AD, we report here the selective immunoisolation of neurotoxic 10&ndas...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Noguchi, A., Matsumura, S., Dezawa, M., Tada, M., Yanazawa, M., Ito, A., Akioka, M., Kikuchi, S., Sato, M., Ideno, S., Noda, M., Fukunari, A., Muramatsu, S.-i., Itokazu, Y., Sato, K., Takahashi, H., Teplow, D. B., Nabeshima, Y.-i., Kakita, A., Imahori, K. Tags: Protein Structure and Folding Source Type: journals
Elevation of Glutamine Level by Selenophosphate Synthetase 1 Knockdown Induces Megamitochondrial Formation in Drosophila Cells [Metabolism and Bioenergetics]Email this article to a colleague.
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Although selenophosphate synthetase 1 (SPS1/SelD) is an essential gene in Drosophila, its function has not been determined. To elucidate its intracellular role, we targeted the removal of SPS1/SelD mRNA in Drosophila SL2 cells using RNA interference technology that led to the formation of vacuole-like globular structures. Surprisingly, these structures were identified as megamitochondria, and only depolarized mitochondria developed into megamitochondria. The mRNA levels of l(2)01810 and glutamine synthetase 1 (GS1) were increased by SPS1/SelD knockdown. Blocking the expression of GS1 and l(2)01810 completely inhibited the ...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Shim, M. S., Kim, J. Y., Jung, H. K., Lee, K. H., Xu, X.-M., Carlson, B. A., Kim, K. W., Kim, I. Y., Hatfield, D. L., Lee, B. J. Tags: Metabolism and Bioenergetics Source Type: journals
D-AKAP2 Interacts with Rab4 and Rab11 through Its RGS Domains and Regulates Transferrin Receptor Recycling [Membrane Transport, Structure, Function, and Biogenesis]Email this article to a colleague.
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Dual-specific A-kinase-anchoring protein 2 (D-AKAP2/AKAP10), which interacts at its carboxyl terminus with protein kinase A and PDZ domain proteins, contains two tandem regulator of G-protein signaling (RGS) domains for which the binding partners have remained unknown. We show here that these RGS domains interact with Rab11 and GTP-bound Rab4, the first demonstration of RGS domains binding small GTPases. Rab4 and Rab11 help regulate membrane trafficking through the endocytic recycling pathways by recruiting effector proteins to specific membrane domains. Although D-AKAP2 is primarily cytosolic in HeLa cells, a fraction of ...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Eggers, C. T., Schafer, J. C., Goldenring, J. R., Taylor, S. S. Tags: Membrane Transport, Structure, Function, and Biogenesis Source Type: journals
The ATPase Cycle of the Mitotic Motor CENP-E [Enzyme Catalysis and Regulation]Email this article to a colleague.
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We have previously shown that the mitotic motor centrosome protein E (CENP-E) is capable of walking for more than 250 steps on its microtubule track without dissociating. We have examined the kinetics of this molecular motor to see if its enzymology explains this remarkable degree of processivity. We find that like the highly processive transport motor kinesin 1, the enzymatic cycle of CENP-E is characterized by rapid ATP binding, multiple enzymatic turnovers per diffusive encounter, and gating of nucleotide binding. These features endow CENP-E with a high duty cycle, a prerequisite for processivity. However, unlike kinesi...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Rosenfeld, S. S., van Duffelen, M., Behnke-Parks, W. M., Beadle, C., Corrreia, J., Xing, J. Tags: Enzyme Catalysis and Regulation Source Type: journals
A Mycobacterial Cyclic AMP Phosphodiesterase That Moonlights as a Modifier of Cell Wall Permeability [Protein Structure and Folding]Email this article to a colleague.
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We present the crystal structure of the full-length and sole cAMP phosphodiesterase, Rv0805, found in M. tuberculosis, whose orthologs are present only in the genomes of slow growing and pathogenic mycobacteria. The dimeric core catalytic domain of Rv0805 adopts a metallophosphoesterase-fold, and the C-terminal region builds the active site and contributes to multiple substrate utilization. Localization of Rv0805 to the cell wall is dependent on its C terminus, and expression of either wild type or mutationally inactivated Rv0805 in M. smegmatis alters cell permeability to hydrophobic cytotoxic compounds. Rv0805 may theref...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Podobnik, M., Tyagi, R., Matange, N., Dermol, U., Gupta, A. K., Mattoo, R., Seshadri, K., Visweswariah, S. S. Tags: Protein Structure and Folding Source Type: journals
A Sporadic Parkinson Disease Model via Silencing of the Ubiquitin-Proteasome/E3 Ligase Component SKP1A [Molecular Basis Of Cell and Developmental Biology]Email this article to a colleague.
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The aim of this study was to develop a new model of sporadic Parkinson disease (PD) based on silencing of the SKP1A gene, a component of the ubiquitin-proteasome/E3 ligase complex, Skp1, Cullin 1, F-box protein, which was found to be highly decreased in the substantia nigra of sporadic PD patients. Initially, an embryonic mouse substantia nigra-derived cell line (SN4741 cells) was infected with short hairpin RNA lentiviruses encoding the murine transcript of the SKP1A gene or with scrambled vector. SKP1A silencing resulted in increased susceptibility to neuronal damages induced by the parkinsonism-inducing neurotoxin 1-met...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Fishman-Jacob, T., Reznichenko, L., Youdim, M. B. H., Mandel, S. A. Tags: Molecular Basis Of Cell and Developmental Biology Source Type: journals
Two Lysine Residues in the Bacterial Luciferase Mobile Loop Stabilize Reaction Intermediates [Enzyme Catalysis and Regulation]Email this article to a colleague.
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In this study, we attempt to localize the loss of activity observed in the loop deletion mutant to individual residues in the mobile loop. Using alanine mutagenesis, the effects of substitution at 15 of the 29 mobile loop residues were examined. Nine of the point mutants had reduced activity in vivo. Two mutations, K283A and K286A, resulted in a loss in quantum yield comparable with that of the loop deletion mutant. The bioluminescence emission spectrum of both mutants was normal, and both yielded the carboxylic acid chemical product at the same efficiency as the wild-type enzyme. Substitution of Lys283 with alanine result...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Campbell, Z. T., Baldwin, T. O. Tags: Enzyme Catalysis and Regulation Source Type: journals
Alternative mRNA Splicing Produces a Novel Biologically Active Short Isoform of PGC-1{alpha} [Metabolism and Bioenergetics]Email this article to a colleague.
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We report here a novel truncated form of PGC-1 (NT-PGC-1) produced by alternative 3' splicing that introduces an in-frame stop codon into PGC-1 mRNA. The expressed protein includes the first 267 amino acids of PGC-1 and 3 additional amino acids from the splicing insert. NT-PGC-1 contains the transactivation and nuclear receptor interaction domains but is missing key domains involved in nuclear localization, interaction with other transcription factors, and protein degradation. Expression and subcellular localization of NT-PGC-1 are dynamically regulated in the context of physiological signals that regulate full-length PGC-...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Zhang, Y., Huypens, P., Adamson, A. W., Chang, J. S., Henagan, T. M., Boudreau, A., Lenard, N. R., Burk, D., Klein, J., Perwitz, N., Shin, J., Fasshauer, M., Kralli, A., Gettys, T. W. Tags: Metabolism and Bioenergetics Source Type: journals
A Distributed Set of Interactions Controls {micro}2 Functionality in the Role of AP-2 as a Sorting Adaptor in Synaptic Vesicle Endocytosis [Membrane Transport, Structure, Function, and Biogenesis]Email this article to a colleague.
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The mechanisms of how, following exocytosis, the approximately nine types of synaptic vesicle (SV) transmembrane proteins are accurately resorted to form SVs are poorly understood. The time course of SV endocytosis is very sensitive to perturbations in clathrin and dynamin, supporting the model that SV endocytosis occurs through a clathrin-mediated pathway. We recently demonstrated that removal of the clathrin adaptor protein AP-2, the key protein thought to coordinate cargo selection into clathrin-coated pits, results in a significant impairment in endocytosis kinetics. Endocytosis, however, still proceeds in the absence ...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Kim, S. H., Ryan, T. A. Tags: Membrane Transport, Structure, Function, and Biogenesis Source Type: journals
Thymidine Analogue Resistance Suppression by V75I of HIV-1 Reverse Transcriptase: EFFECTS OF SUBSTITUTING VALINE 75 ON STAVUDINE EXCISION AND DISCRIMINATION [Enzyme Catalysis and Regulation]Email this article to a colleague.
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Val75 of HIV-1 reverse transcriptase (RT) plays a role in positioning the template nucleotide +1 during the formation of the ternary complex. Mutations, such as V75M and V75A, emerge in patients infected with HIV-1 group M subtype B and group O variants, after failing treatment with stavudine (d4T) and other nucleoside RT inhibitors. V75I is an accessory mutation of the Q151M multidrug resistance complex of HIV-1 RT and is rarely associated with thymidine analogue resistance mutations (TAMs). In vitro, it confers resistance to acyclovir. TAMs confer resistance to zidovudine (AZT) and d4T by increasing the rate of ATP-media...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Matamoros, T., Nevot, M., Martinez, M. A., Menendez-Arias, L. Tags: Enzyme Catalysis and Regulation Source Type: journals
Involvement of the {beta} Clamp in Methyl-directed Mismatch Repair in Vitro [Dna: Replication, Repair, Recombination, and Chromosome Dynamics]Email this article to a colleague.
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We have examined function of the bacterial β replication clamp in the different steps of methyl-directed DNA mismatch repair. The mismatch-, MutS-, and MutL-dependent activation of MutH is unaffected by the presence or orientation of loaded β clamp on either 3' or 5' heteroduplexes. Similarly, β is not required for 3' or 5' mismatch-provoked excision when scored in the presence of complex or in the presence of complex and DNA polymerase III core components. However, mismatch repair does not occur in the absence of β, an effect we attribute to a requirement for the clamp in the repair DNA synthesis step ...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Pluciennik, A., Burdett, V., Lukianova, O., O'Donnell, M., Modrich, P. Tags: Dna: Replication, Repair, Recombination, and Chromosome Dynamics Source Type: journals
PGRL1 Participates in Iron-induced Remodeling of the Photosynthetic Apparatus and in Energy Metabolism in Chlamydomonas reinhardtii [Metabolism and Bioenergetics]Email this article to a colleague.
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PGRL1 RNA and protein levels are increased in iron-deficient Chlamydomonas reinhardtii cells. In an RNAi strain, which accumulates lower PGRL1 levels in both iron-replete and -starved conditions, the photosynthetic electron transfer rate is decreased, respiratory capacity in iron-sufficient conditions is increased, and the efficiency of cyclic electron transfer under iron-deprivation is diminished. Pgrl1-kd cells exhibit iron deficiency symptoms at higher iron concentrations than wild-type cells, although the cells are not more depleted in cellular iron relative to wild-type cells as measured by mass spectrometry. Thiol-tr...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Petroutsos, D., Terauchi, A. M., Busch, A., Hirschmann, I., Merchant, S. S., Finazzi, G., Hippler, M. Tags: Metabolism and Bioenergetics Source Type: journals
Three-way Interaction between 14-3-3 Proteins, the N-terminal Region of Tyrosine Hydroxylase, and Negatively Charged Membranes [Lipids and Lipoproteins: Metabolism, Regulation, and Signaling]Email this article to a colleague.
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Tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines, is activated by phosphorylation-dependent binding to 14-3-3 proteins. The N-terminal domain of TH is also involved in interaction with lipid membranes. We investigated the binding of the N-terminal domain to its different partners, both in the unphosphorylated (TH-(1–43)) and Ser19-phosphorylated (THp-(1–43)) states by surface plasmon resonance. THp-(1–43) showed high affinity for 14-3-3 proteins (Kd ~ 0.5 µm for 14-3-3 and - and 7 µm for 14-3-3). The domains also bind to negatively charged membranes with i...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Halskau, O., Ying, M., Baumann, A., Kleppe, R., Rodriguez-Larrea, D., Almas, B., Haavik, J., Martinez, A. Tags: Lipids and Lipoproteins: Metabolism, Regulation, and Signaling Source Type: journals
Domain II Loop 3 of Bacillus thuringiensis Cry1Ab Toxin Is Involved in a "Ping Pong" Binding Mechanism with Manduca sexta Aminopeptidase-N and Cadherin Receptors [Protein Structure and Folding]Email this article to a colleague.
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Bacillus thuringiensis Cry toxins are used worldwide as insecticides in agriculture, in forestry, and in the control of disease transmission vectors. In the lepidopteran Manduca sexta, cadherin (Bt-R1) and aminopeptidase-N (APN) function as Cry1A toxin receptors. The interaction with Bt-R1 promotes cleavage of the amino-terminal end, including helix -1 and formation of prepore oligomer that binds to APN, leading to membrane insertion and pore formation. Loops of domain II of Cry1Ab toxin are involved in receptor interaction. Here we show that Cry1Ab mutants located in domain II loop 3 are affected in binding to both recept...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Pacheco, S., Gomez, I., Arenas, I., Saab-Rincon, G., Rodriguez-Almazan, C., Gill, S. S., Bravo, A., Soberon, M. Tags: Protein Structure and Folding Source Type: journals
GCN2 Protein Kinase Is Required to Activate Amino Acid Deprivation Responses in Mice Treated with the Anti-cancer Agent L-Asparaginase [Mechanisms Of Signal Transduction]Email this article to a colleague.
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The objectives of this study were to assess the role of the eIF2 kinases and protein kinase R-like endoplasmic reticulum resident kinase (PERK) in controlling AADR to asparaginase and to compare the effects of asparaginase on mTORC1 to that of rapamycin. In experiment 1, asparaginase increased hepatic p-eIF2 in wild-type mice and mice with a liver-specific PERK deletion but not in GCN2 null mice nor in GCN2-PERK double null livers. In experiment 2, wild-type and GCN2 null mice were treated with asparaginase (3 IU per g of body weight), rapamycin (2 mg per kg of body weight), or both. In wild-type mice, asparaginase but not...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Bunpo, P., Dudley, A., Cundiff, J. K., Cavener, D. R., Wek, R. C., Anthony, T. G. Tags: Mechanisms Of Signal Transduction Source Type: journals
Roles of Two Ca2+-binding Domains in Regulation of the Cardiac Na+-Ca2+ Exchanger [Membrane Transport, Structure, Function, and Biogenesis]Email this article to a colleague.
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We expressed full-length Na+-Ca2+ exchangers (NCXs) with mutations in two Ca2+-binding domains (CBD1 and CBD2) to determine the roles of the CBDs in Ca2+-dependent regulation of NCX. CBD1 has four Ca2+-binding sites, and mutation of residues Asp421 and Glu451, which primarily coordinate Ca2+ at sites 1 and 2, had little effect on regulation of NCX by Ca2+. In contrast, mutations at residues Glu385, Asp446, Asp447, and Asp500, which coordinate Ca2+ at sites 3 and 4 of CBD1, resulted in a drastic decrease in the apparent affinity of peak exchange current for regulatory Ca2+. Another mutant, M7, with 7 key residues of CBD1 re...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Ottolia, M., Nicoll, D. A., Philipson, K. D. Tags: Membrane Transport, Structure, Function, and Biogenesis Source Type: journals
Role of Spike Protein Endodomains in Regulating Coronavirus Entry [Protein Structure and Folding]Email this article to a colleague.
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Enveloped viruses enter cells by viral glycoprotein-mediated binding to host cells and subsequent fusion of virus and host cell membranes. For the coronaviruses, viral spike (S) proteins execute these cell entry functions. The S proteins are set apart from other viral and cellular membrane fusion proteins by their extensively palmitoylated membrane-associated tails. Palmitate adducts are generally required for protein-mediated fusions, but their precise roles in the process are unclear. To obtain additional insights into the S-mediated membrane fusion process, we focused on these acylated carboxyl-terminal intravirion tail...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Shulla, A., Gallagher, T. Tags: Protein Structure and Folding Source Type: journals
A New Model for the Transition of APAF-1 from Inactive Monomer to Caspase-activating Apoptosome [Mechanisms Of Signal Transduction]Email this article to a colleague.
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The cytosolic adaptor protein Apaf-1 is a key player in the intrinsic pathway of apoptosis. Binding of mitochondrially released cytochrome c and of dATP or ATP to Apaf-1 induces the formation of the heptameric apoptosome complex, which in turn activates procaspase-9. We have re-investigated the chain of events leading from monomeric autoinhibited Apaf-1 to the functional apoptosome in vitro. We demonstrate that Apaf-1 does not require energy from nucleotide hydrolysis to eventually form the apoptosome. Despite a low intrinsic hydrolytic activity of the autoinhibited Apaf-1 monomer, nucleotide hydrolysis does not occur at a...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Reubold, T. F., Wohlgemuth, S., Eschenburg, S. Tags: Mechanisms Of Signal Transduction Source Type: journals
Crystal Structure and Catalytic Mechanism of 4-Methylmuconolactone Methylisomerase [Protein Structure and Folding]Email this article to a colleague.
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When methyl-substituted aromatic compounds are degraded via ortho (intradiol)-cleavage of 4-methylcatechol, the dead-end metabolite 4-methylmuconolactone (4-ML) is formed. Degradation of 4-ML has only been described in few bacterial species, including Pseudomonas reinekei MT1. The isomerization of 4-ML to 3-methylmuconolactone (3-ML) is the first step required for the mineralization of 4-ML and is catalyzed by an enzyme termed 4-methylmuconolactone methylisomerase (MLMI). We identified the gene encoding MLMI in P. reinekei MT1 and solved the crystal structures of MLMI in complex with 3-ML at 1.4-Å resolution, with 4-...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Marin, M., Heinz, D. W., Pieper, D. H., Klink, B. U. Tags: Protein Structure and Folding Source Type: journals
Mechanistic Details of Glutathione Biosynthesis Revealed by Crystal Structures of Saccharomyces cerevisiae Glutamate Cysteine Ligase [Protein Structure and Folding]Email this article to a colleague.
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Glutathione is a thiol-disulfide exchange peptide critical for buffering oxidative or chemical stress, and an essential cofactor in several biosynthesis and detoxification pathways. The rate-limiting step in its de novo biosynthesis is catalyzed by glutamate cysteine ligase, a broadly expressed enzyme for which limited structural information is available in higher eukaryotic species. Structural data are critical to the understanding of clinical glutathione deficiency, as well as rational design of enzyme modulators that could impact human disease progression. Here, we have determined the structures of Saccharomyces cerevis...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Biterova, E. I., Barycki, J. J. Tags: Protein Structure and Folding Source Type: journals
A Novel Role for hGas7b in Microtubular Maintenance: POSSIBLE IMPLICATION IN TAU-ASSOCIATED PATHOLOGY IN ALZHEIMER DISEASE [Molecular Basis Of Cell and Developmental Biology]Email this article to a colleague.
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Here, we report a novel role for hGas7b (human growth arrest specific protein 7b) in the regulation of microtubules. Using a bioinformatic approach, we studied the actin-binding protein hGas7b with a structural similarity to the WW domain of a peptidyl prolyl cis/trans isomerase, Pin1, that facilitates microtubule assembly. Thus, we have demonstrated that hGas7b binds Tau at the WW motif and that the hGas7b/Tau protein complex interacts with the microtubules, promoting tubulin polymerization. Tau, in turn, contributes to protein stability of hGas7b. Furthermore, we observed decreased levels of hGas7b in the brains from pat...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Akiyama, H., Gotoh, A., Shin, R.-W., Koga, T., Ohashi, T., Sakamoto, W., Harada, A., Arai, H., Sawa, A., Uchida, C., Uchida, T. Tags: Molecular Basis Of Cell and Developmental Biology Source Type: journals
Discovery and Investigation of Misincorporation of Serine at Asparagine Positions in Recombinant Proteins Expressed in Chinese Hamster Ovary Cells [Protein Synthesis, Post-Translational Modification, and Degradation]Email this article to a colleague.
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Misincorporation of amino acids in proteins expressed in Escherichia coli has been well documented but not in proteins expressed in mammalian cells under normal recombinant protein production conditions. Here we report for the first time that Ser can be incorporated at Asn positions in proteins expressed in Chinese hamster ovary cells. This misincorporation was discovered as a result of intact mass measurement, peptide mapping analysis, and tandem mass spectroscopy sequencing. Our analyses showed that the substitution was not related to specific protein molecules or DNA codons and was not site-specific. We believe that the...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Wen, D., Vecchi, M. M., Gu, S., Su, L., Dolnikova, J., Huang, Y.-M., Foley, S. F., Garber, E., Pederson, N., Meier, W. Tags: Protein Synthesis, Post-Translational Modification, and Degradation Source Type: journals
Membrane Rafts Are Involved in Intracellular Miconazole Accumulation in Yeast Cells [Lipids and Lipoproteins: Metabolism, Regulation, and Signaling]Email this article to a colleague.
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Azoles inhibit ergosterol biosynthesis, resulting in ergosterol depletion and accumulation of toxic 14-methylated sterols in membranes of susceptible yeast. We demonstrated previously that miconazole induces actin cytoskeleton stabilization in Saccharomyces cerevisiae prior to induction of reactive oxygen species, pointing to an ancillary mode of action. Using a genome-wide agar-based screening, we demonstrate in this study that S. cerevisiae mutants affected in sphingolipid and ergosterol biosynthesis, namely ipt1, sur1, skn1, and erg3 deletion mutants, are miconazole-resistant, suggesting an involvement of membrane rafts...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Francois, I. E. J. A., Bink, A., Vandercappellen, J., Ayscough, K. R., Toulmay, A., Schneiter, R., van Gyseghem, E., Van den Mooter, G., Borgers, M., Vandenbosch, D., Coenye, T., Cammue, B. P. A., Thevissen, K. Tags: Lipids and Lipoproteins: Metabolism, Regulation, and Signaling Source Type: journals
Localization, Purification, and Functional Reconstitution of the P4-ATPase Atp8a2, a Phosphatidylserine Flippase in Photoreceptor Disc Membranes [Membrane Transport, Structure, Function, and Biogenesis]Email this article to a colleague.
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In this study, we report on the localization and functional properties of Atp8a2, a member of the P4-ATPase subfamily that has not been studied previously. Reverse transcription-PCR revealed high expression of atp8a2 mRNA in the retina and testis. Within the retina, immunofluorescence microscopy and subcellular fractionation studies localized Atp8a2 to outer segment disc membranes of rod and cone photoreceptor cells. Atp8a2 purified from photoreceptor outer segments by immunoaffinity chromatography exhibited ATPase activity that was stimulated by phosphatidylserine and to a lesser degree phosphatidylethanolamine but not by...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Coleman, J. A., Kwok, M. C. M., Molday, R. S. Tags: Membrane Transport, Structure, Function, and Biogenesis Source Type: journals
Characterization of Human Cone Phosphodiesterase-6 Ectopically Expressed in Xenopus laevis Rods [Mechanisms Of Signal Transduction]Email this article to a colleague.
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PDE6 (phosphodiesterase-6) is the effector molecule in the vertebrate phototransduction cascade. Progress in understanding the structure and function of PDE6 has been hindered by lack of an expression system of the enzyme. Here we report ectopic expression and analysis of compartmentalization and membrane dynamics of the enhanced green fluorescent protein (EGFP) fusion protein of human cone PDE6C in rods of transgenic Xenopus laevis. EGFP-PDE6C is correctly targeted to the rod outer segments in transgenic Xenopus, where it displayed a characteristic striated pattern of EGFP fluorescence. Immunofluorescence labeling indicat...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Muradov, H., Boyd, K. K., Haeri, M., Kerov, V., Knox, B. E., Artemyev, N. O. Tags: Mechanisms Of Signal Transduction Source Type: journals
Interactions between EB1 and Microtubules: DRAMATIC EFFECT OF AFFINITY TAGS AND EVIDENCE FOR COOPERATIVE BEHAVIOR [Molecular Basis Of Cell and Developmental Biology]Email this article to a colleague.
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Plus end tracking proteins (+TIPs) are a unique group of microtubule binding proteins that dynamically track microtubule (MT) plus ends. EB1 is a highly conserved +TIP with a fundamental role in MT dynamics, but it remains poorly understood in part because reported EB1 activities have differed considerably. One reason for this inconsistency could be the variable presence of affinity tags used for EB1 purification. To address this question and establish the activity of native EB1, we have measured the MT binding and tubulin polymerization activities of untagged EB1 and EB1 fragments and compared them with those of His-tagge...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Zhu, Z. C., Gupta, K. K., Slabbekoorn, A. R., Paulson, B. A., Folker, E. S., Goodson, H. V. Tags: Molecular Basis Of Cell and Developmental Biology Source Type: journals
Identification of a New Exosite Involved in Catalytic Turnover by the Streptokinase-Plasmin Activator Complex during Human Plasminogen Activation [Enzyme Catalysis and Regulation]Email this article to a colleague.
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With the goal of identifying hitherto unknown surface exosites of streptokinase involved in substrate human plasminogen recognition and catalytic turnover, synthetic peptides encompassing the 170 loop (CQFTPLNPDDDFRPGLKDTKLLC) in the β-domain were tested for selective inhibition of substrate human plasminogen activation by the streptokinase-plasmin activator complex. Although a disulfide-constrained peptide exhibited strong inhibition, a linear peptide with the same sequence, or a disulfide-constrained variant with a single lysine to alanine mutation showed significantly reduced capabilities of inhibition. Alanine-sca...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Aneja, R., Datt, M., Singh, B., Kumar, S., Sahni, G. Tags: Enzyme Catalysis and Regulation Source Type: journals
Transcriptional Regulation of Mouse Mast Cell Protease-2 by Interleukin-15 [Transcription, Chromatin, and Epigenetics]Email this article to a colleague.
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Mast cells (MCs) play a critical role in innate and adaptive immunity through the release of cytokines, chemokines, lipid mediators, biogenic amines, and proteases. We recently showed that the activities of MC proteases are transcriptionally regulated by intracellularly retained interleukin-15 (IL-15), and we provided evidence that this cytokine acts as a specific regulator of mouse mast cell protease-2 (mMCP-2). Here, we show that in wild-type bone marrow-derived mast cells (BMMCs) IL-15 inhibits mMCP-2 transcription indirectly by inducing differential expression and mMCP-2 promoter binding of the bifunctional transcripti...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Mirghomizadeh, F., Bullwinkel, J., Orinska, Z., Janssen, O., Petersen, A., Singh, P. B., Bulfone-Paus, S. Tags: Transcription, Chromatin, and Epigenetics Source Type: journals
Saccharomyces CDK1 Phosphorylates Rad53 Kinase in Metaphase, Influencing Cellular Morphogenesis [Mechanisms Of Signal Transduction]Email this article to a colleague.
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Rad53 is an essential protein kinase governing DNA damage and replication stress checkpoints in budding yeast. It also appears to be involved in cellular morphogenesis processes. Mass spectrometry analyses revealed that Rad53 is phosphorylated at multiple SQ/TQ and at SP/TP residues, which are typical consensus sites for phosphatidylinositol 3-kinase-related kinases and CDKs, respectively. Here we show that Clb-CDK1 phosphorylates Rad53 at Ser774 in metaphase. This phosphorylation event does not influence the DNA damage and replication checkpoint roles of Rad53, and it is independent of the spindle assembly checkpoint netw...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Diani, L., Colombelli, C., Nachimuthu, B. T., Donnianni, R., Plevani, P., Muzi-Falconi, M., Pellicioli, A. Tags: Mechanisms Of Signal Transduction Source Type: journals
Phosphorylation of Neuronal Survival Factor MEF2D by Glycogen Synthase Kinase 3{beta} in Neuronal Apoptosis [Mechanisms Of Signal Transduction]Email this article to a colleague.
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We reported here that myocyte enhancer factor 2D (MEF2D), a nuclear transcription factor known to promote neuronal survival, is directly phosphorylated by GSK3β. Our data showed that phosphorylation of MEF2D by GSK3β at three specific residues in its transactivation domain inhibits MEF2D transcriptional activity. Withdrawal of neuronal activity in cerebellar granule neurons activated GSK3β in the nucleus, leading to GSK3β-dependent inhibition of MEF2 function. This inhibition contributed to GSK3β-mediated neuronal toxicity. Overexpression of MEF2D mutant that is resistant to GSK3β inhibition p...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Wang, X., She, H., Mao, Z. Tags: Mechanisms Of Signal Transduction Source Type: journals
Von Hippel-Lindau Gene Product Modulates TIS11B Expression in Renal Cell Carcinoma: IMPACT ON VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION IN HYPOXIA [Mechanisms Of Signal Transduction]Email this article to a colleague.
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TIS11B belongs to a group of RNA-binding proteins (including TIS11/tristetraprolin and TIS11D) that share characteristic tandem CCCH-type zinc-finger domains and can be rapidly induced by multiple stimuli. TIS11B has been shown to regulate vascular endothelial growth factor (VEGF) mRNA stability in adrenocorticotropic hormone-stimulated primary adrenocortical cells. TIS11B has also been documented as a negative regulator of VEGF during development, but nothing has yet been reported in the context of human cancers. The Von Hippel-Lindau (VHL) tumor suppressor protein regulates VEGF gene expression at both the transcriptiona...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Sinha, S., Dutta, S., Datta, K., Ghosh, A. K., Mukhopadhyay, D. Tags: Mechanisms Of Signal Transduction Source Type: journals
Differential Involvement of Atg16L1 in Crohn Disease and Canonical Autophagy: ANALYSIS OF THE ORGANIZATION OF THE Atg16L1 COMPLEX IN FIBROBLASTS [Membrane Transport, Structure, Function, and Biogenesis]Email this article to a colleague.
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A single nucleotide polymorphism in Atg16L1, an autophagy-related gene (ATG), is a risk factor for Crohn disease, a major form of chronic inflammatory bowel disease. However, it is still unknown how the Atg16L1 variant contributes to disease development. The Atg16L1 protein possesses a C-terminal WD repeat domain whose function is entirely unknown, and the Crohn disease-associated mutation (T300A) is within this domain. To elucidate the function of the WD repeat domain, we established an experimental system in which a WD repeat domain mutant of Atg16L1 is stably expressed in Atg16L1-deficient mouse embryonic fibroblasts. U...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Fujita, N., Saitoh, T., Kageyama, S., Akira, S., Noda, T., Yoshimori, T. Tags: Membrane Transport, Structure, Function, and Biogenesis Source Type: journals
The Endoplasmic Reticulum of Dorsal Root Ganglion Neurons Contains Functional TRPV1 Channels [Mechanisms Of Signal Transduction]Email this article to a colleague.
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Transient receptor potential vanilloid type 1 (TRPV1) is a plasma membrane Ca2+ channel involved in transduction of painful stimuli. Dorsal root ganglion (DRG) neurons express ectopic but functional TRPV1 channels in the endoplasmic reticulum (ER) (TRPV1ER). We have studied the properties of TRPV1ER in DRG neurons and HEK293T cells expressing TRPV1. Activation of TRPV1ER with capsaicin or other vanilloids produced an increase of cytosolic Ca2+ due to Ca2+ release from the ER. The decrease of [Ca2+]ER was directly revealed by an ER-targeted aequorin Ca2+ probe, expressed in DRG neurons using a herpes amplicon virus. The sen...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Gallego-Sandin, S., Rodriguez-Garcia, A., Alonso, M. T., Garcia-Sancho, J. Tags: Mechanisms Of Signal Transduction Source Type: journals
Myocardin-dependent Activation of the CArG Box-rich Smooth Muscle {gamma}-Actin Gene: PREFERENTIAL UTILIZATION OF A SINGLE CArG ELEMENT THROUGH FUNCTIONAL ASSOCIATION WITH THE NKX3.1 HOMEODOMAIN PROTEIN [Transcription, Chromatin, and Epigenetics]Email this article to a colleague.
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Serum response factor (SRF) is a ubiquitously expressed transcription factor that binds a 10-bp element known as the CArG box, located in the proximal regulatory region of hundreds of target genes. SRF activates target genes in a cell- and context-dependent manner by assembling unique combinations of cofactors over CArG elements. One particularly strong SRF cofactor, myocardin (MYOCD), acts as a component of a molecular switch for smooth muscle cell (SMC) differentiation by activating cytoskeletal and contractile genes harboring SRF-binding CArG elements. Here we report that the human ACTG2 promoter, containing four conser...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Sun, Q., Taurin, S., Sethakorn, N., Long, X., Imamura, M., Wang, D.-Z., Zimmer, W. E., Dulin, N. O., Miano, J. M. Tags: Transcription, Chromatin, and Epigenetics Source Type: journals
Yeast Colony Survival Depends on Metabolic Adaptation and Cell Differentiation Rather Than on Stress Defense [Metabolism and Bioenergetics]Email this article to a colleague.
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Enzymes scavenging reactive oxygen species (ROS) are important for cell protection during stress and aging. A deficiency in these enzymes leads to ROS imbalance, causing various disorders in many organisms, including yeast. In contrast to liquid cultures, where fitness of the yeast population depends on its ROS scavenging capability, the present study suggests that Saccharomyces cerevisiae cells growing in colonies capable of ammonia signaling use a broader protective strategy. Instead of maintaining high levels of antioxidant enzymes for ROS detoxification, colonies activate an alternative metabolism that prevents ROS pro...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Cap, M., Vachova, L., Palkova, Z. Tags: Metabolism and Bioenergetics Source Type: journals
Heparan Sulfate and Transglutaminase Activity Are Required for the Formation of Covalently Cross-linked Hedgehog Oligomers [Glycobiology and Extracellular Matrices]Email this article to a colleague.
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Sonic hedgehog (Shh) signaling plays major roles in embryonic development and has also been associated with the progression of certain cancers. Here, Shh family members act directly as long range morphogens, and their ability to do so has been linked to the formation of freely diffusible multimers from the lipidated, cell-tethered monomer (ShhNp). In this work we demonstrate that the multimeric morphogen secreted from endogenous sources, such as mouse embryos and primary chick chondrocytes, consists of oligomeric substructures that are "undisruptable" by boiling, denaturants, and reducing agents. Undisruptable (UD) morphog...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Dierker, T., Dreier, R., Migone, M., Hamer, S., Grobe, K. Tags: Glycobiology and Extracellular Matrices Source Type: journals
Different Strategies Adopted by Kb and Ld to Generate T Cell Specificity Directed against Their Respective Bound Peptides [Protein Structure and Folding]Email this article to a colleague.
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Mouse T cell clone 2C recognizes two different major histocompatibility (MHC) ligands, the self MHC Kb and the allogeneic MHC Ld. Two distinct peptides, SIY (SIYRYYGL) and QL9 (QLSPFPFDL), act as strong and specific agonists when bound to Kb and Ld, respectively. To explore further the mechanisms involved in peptide potency and specificity, here we examined a collection of single amino acid peptide variants of SIY and QL9 for 1) T cell activity, 2) binding to their respective MHC, and 3) binding to the 2C T cell receptor (TCR) and high affinity TCR mutants. Characterization of SIY binding to MHC Kb revealed significant eff...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Bowerman, N. A., Colf, L. A., Garcia, K. C., Kranz, D. M. Tags: Protein Structure and Folding Source Type: journals
Blocking L-type Voltage-gated Ca2+ Channels with Dihydropyridines Reduces {gamma}-Aminobutyric Acid Type A Receptor Expression and Synaptic Inhibition [Membrane Transport, Structure, Function, and Biogenesis]Email this article to a colleague.
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-Aminobutyric acid type A receptors (GABAARs) are the major sites of fast inhibitory neurotransmission in the brain, and the numbers of these receptors at the cell surface can determine the strength of GABAergic neurotransmission. Chronic changes in neuronal activity lead to an adaptive modulation in the efficacy of GABAergic synaptic inhibition, brought about in part by changes in the number of synaptic GABAARs, a mechanism known as homeostatic synaptic plasticity. Reduction in the number of GABAARs in response to prolonged neuronal activity blockade is dependent on the ubiquitin-proteasome system. The underlying biochemi...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Saliba, R. S., Gu, Z., Yan, Z., Moss, S. J. Tags: Membrane Transport, Structure, Function, and Biogenesis Source Type: journals
Identification and Functional Characterization of ERK/MAPK Phosphorylation Sites in the Runx2 Transcription Factor [Transcription, Chromatin, and Epigenetics]Email this article to a colleague.
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In this study, we used a combination of in vitro and in vivo phosphorylation analysis, mass spectroscopy, and functional assays to identify two sites at Ser301 and Ser319 within the proline/serine/threonine domain of Runx2 that are required for this regulation. These sites are phosphorylated by activated ERK1 in vitro and in cell culture. In addition to confirming ERK-dependent phosphorylation at Ser319, mass spectroscopy identified two other ERK-phosphorylated sites at Ser43 and Ser510. Furthermore, introduction of S301A,S319A mutations rendered Runx2 resistant to MAPK-dependent activation and reduced its ability to stimu...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Ge, C., Xiao, G., Jiang, D., Yang, Q., Hatch, N. E., Roca, H., Franceschi, R. T. Tags: Transcription, Chromatin, and Epigenetics Source Type: journals
Depletion of Selenoprotein GPx4 in Spermatocytes Causes Male Infertility in Mice [Lipids and Lipoproteins: Metabolism, Regulation, and Signaling]Email this article to a colleague.
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Phospholipid hydroperoxide glutathione peroxidase (GPx4) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids. GPx4 is strongly expressed in the mitochondria of testis and spermatozoa. We previously found a significant decrease in the expression of GPx4 in spermatozoa from 30% of infertile human males diagnosed with oligoasthenozoospermia (Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M., and Nakagawa, Y. (2001) Biol. Reprod. 64, 674–683). To clarify whether defective GPx4 in spermatocytes causes male infertility, we established spermato...
Source: Journal of Biological Chemistry - November 13, 2009 Category: Chemistry Authors: Imai, H., Hakkaku, N., Iwamoto, R., Suzuki, J., Suzuki, T., Tajima, Y., Konishi, K., Minami, S., Ichinose, S., Ishizaka, K., Shioda, S., Arata, S., Nishimura, M., Naito, S., Nakagawa, Y. Tags: Lipids and Lipoproteins: Metabolism, Regulation, and Signaling Source Type: journals
