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Infrared spectroscopy aids cancer diagnosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A genetic algorithm developed by UK scientists could aid the use of infrared spectroscopy in cancer diagnosis (Source: Chemistry World | Latest News)
Source: Chemistry World | Latest News - March 19, 2010 Category: Chemistry Source Type: journals

Dual sensing spray-on wash-off paintsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A water-based fluorescent paint simultaneously images pressure and temperature distribution on aeroplanes and cars (Source: Chemistry World | Latest News)
Source: Chemistry World | Latest News - March 19, 2010 Category: Chemistry Source Type: journals

New self-replication system governed by mechanical forceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Shaken or stirred? Chemists discover a new self-replication system whose outcome is dictated by how mechanical force is applied to it (Source: Chemistry World | Latest News)
Source: Chemistry World | Latest News - March 19, 2010 Category: Chemistry Source Type: journals

Lipid-based drug carriers target tumoursEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A unique way to control the size of lipid-based anticancer drug carriers could lead to more efficient anticancer therapy (Source: Chemistry World | Latest News)
Source: Chemistry World | Latest News - March 19, 2010 Category: Chemistry Source Type: journals

Reach deadline at riskEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chemicals at risk of being removed from market as large number of firms look set to miss EU chemical regulation deadline (Source: Chemistry World | Latest News)
Source: Chemistry World | Latest News - March 19, 2010 Category: Chemistry Source Type: journals

GET with the Complex{diamondsuit}: Crystal Structure of Get4-Get5 Complex and Its Interactions with Sgt2, Get3, and Ydj1 [Papers Of The Week]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Tags: Papers Of The Week Source Type: journals

Hydrophobic Side Chain Dynamics of a Glutamate Receptor Ligand Binding Domain [Neurobiology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ionotropic glutamate receptors are ligand-gated ion channels that mediate much of the fast excitatory neurotransmission in the central nervous system. The extracellular ligand binding core (S1S2) of the GluR2 subtype of ionotropic glutamate receptors can be produced as a soluble protein with properties essentially identical to the corresponding domain in the intact, membrane-bound protein. Using a variety of biophysical techniques, much has been learned about the structure and dynamics of S1S2 and the relationship between its ligand-induced conformational changes and the function of the receptor. It is clear that dynamic p...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Maltsev, A. S., Oswald, R. E. Tags: Neurobiology Source Type: journals

Ginkgolide X Is a Potent Antagonist of Anionic Cys-loop Receptors with a Unique Selectivity Profile at Glycine Receptors [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The novel ginkgolide analog ginkgolide X was characterized functionally at human glycine and -aminobutyric acid type A receptors (GlyRs and GABAARs, respectively) in the fluorescence-based FLIPRTM Membrane Potential assay. The compound inhibited the signaling of all GABAAR subtypes included in the study with high nanomolar/low micromolar IC50 values, except the 1 receptor at which it was a significantly weaker antagonist. Ginkgolide X also displayed high nanomolar/low micromolar IC50 values at the homomeric 1 and 2 GlyRs, whereas it was inactive at the heteromeric 1β and 2β subtypes at concentrations up to 300 &m...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Jensen, A. A., Bergmann, M. L., Sander, T., Balle, T. Tags: Protein Structure and Folding Source Type: journals

Structure and Filament Dynamics of the pSK41 Actin-like ParM Protein: IMPLICATIONS FOR PLASMID DNA SEGREGATION [Dna and Chromosomes]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type II plasmid partition systems utilize ParM NTPases in coordination with a centromere-binding protein called ParR to mediate accurate DNA segregation, a process critical for plasmid retention. The Staphylococcus aureus pSK41 plasmid is a medically important plasmid that confers resistance to multiple antibiotics, disinfectants, and antiseptics. In the first step of partition, the pSK41 ParR binds its DNA centromere to form a superhelical partition complex that recruits ParM, which then mediates plasmid separation. pSK41 ParM is homologous to R1 ParM, a known actin homologue, suggesting that it may also form filaments to...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Popp, D., Xu, W., Narita, A., Brzoska, A. J., Skurray, R. A., Firth, N., Goshdastider, U., Maeda, Y., Robinson, R. C., Schumacher, M. A. Tags: Dna and Chromosomes Source Type: journals

Src Kinase Phosphorylates RUNX3 at Tyrosine Residues and Localizes the Protein in the Cytoplasm [Molecular Bases Of Disease]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we found that the overexpression of Src results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3. We also found that the tyrosine residues of endogenous RUNX3 are phosphorylated and that the protein is localized in the cytoplasm in Src-activated cancer cell lines. We further showed that the knockdown of Src by small interfering RNA, or the inhibition of Src kinase activity by a chemical inhibitor, causes the re-localization of RUNX3 to the nucleus. Collectively, our results demonstrate that the tyrosine phosphorylation of RUNX3 by activated Src is associated with the cytoplasmic localiza...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Goh, Y.-M., Cinghu, S., Hong, E. T. H., Lee, Y.-S., Kim, J.-H., Jang, J.-W., Li, Y.-H., Chi, X.-Z., Lee, K.-S., Wee, H., Ito, Y., Oh, B.-C., Bae, S.-C. Tags: Molecular Bases Of Disease Source Type: journals

Gated Access to the Pore of a P2X Receptor: STRUCTURAL IMPLICATIONS FOR CLOSED-OPEN TRANSITIONS [Molecular Biophysics]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we quantified gated access to Cd2+ at substituted cysteines in TM2 of P2X2 receptors in the open and closed states. Our data for the closed state are consistent with the zebrafish P2X4.1 structure, with isoleucines and threonines (Ile-332 and Thr-336) positioned one helical turn apart lining the channel wall on approach to the gate. Our data for the open state reveal gated access to deeper parts of the pore (Thr-339, Val-343, Asp-349, and Leu-353), suggesting the closed channel gate is between Thr-336 and Thr-339. We also found unexpected interactions between native Cys-348 and D349C that result in tight Cd2...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Kracun, S., Chaptal, V., Abramson, J., Khakh, B. S. Tags: Molecular Biophysics Source Type: journals

CB1 Cannabinoid Receptors Increase Neuronal Precursor Proliferation through AKT/Glycogen Synthase Kinase-3{beta}/{beta}-Catenin Signaling [Signal Transduction]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The endocannabinoid system is involved in the regulation of many physiological effects in the central and peripheral nervous system. Recent findings have demonstrated the presence of a functional endocannabinoid system within neuronal progenitors located in the hippocampus and ventricular/subventricular zone that participates in the regulation of cell proliferation. It is presently unknown whether the endocannabinoid system exerts a widespread effect on neuronal precursors from different neurogenic regions, and very little is known about the signaling by which it regulates neuronal precursor proliferation. Herein, we demon...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Trazzi, S., Steger, M., Mitrugno, V. M., Bartesaghi, R., Ciani, E. Tags: Signal Transduction Source Type: journals

Structure of the DNA-bound BRCA1 C-terminal Region from Human Replication Factor C p140 and Model of the Protein-DNA Complex [Dna and Chromosomes]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
BRCA1 C-terminal domain (BRCT)-containing proteins are found widely throughout the animal and bacteria kingdoms where they are exclusively involved in cell cycle regulation and DNA metabolism. Whereas most BRCT domains are involved in protein-protein interactions, a small subset has bona fide DNA binding activity. Here, we present the solution structure of the BRCT region of the large subunit of replication factor C bound to DNA and a model of the structure-specific complex with 5'-phosphorylated double-stranded DNA. The replication factor C BRCT domain possesses a large basic patch on one face, which includes residues tha...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Kobayashi, M., AB, E., Bonvin, A. M. J. J., Siegal, G. Tags: Dna and Chromosomes Source Type: journals

Stefin B Interacts with Histones and Cathepsin L in the Nucleus [Enzymology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases localized in the nucleus and the cytosol. Loss-of-function mutations in the stefin B gene (CSTB) gene were reported in patients with Unverricht-Lundborg disease (EPM1). We have identified an interaction between stefin B and nucleosomes, specifically with histones H2A.Z, H2B, and H3. In synchronized T98G cells, stefin B co-immunoprecipitated with histone H3, predominantly in the G1 phase of the cell cycle. Stefin B-deficient mouse embryonic fibroblasts entered S phase earlier than wild type mouse embryonic fibroblasts. In contrast, increased expression...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Ceru, S., Konjar, S., Maher, K., Repnik, U., Krizaj, I., Bencina, M., Renko, M., Nepveu, A., Zerovnik, E., Turk, B., Kopitar-Jerala, N. Tags: Enzymology Source Type: journals

Histone Deacetylase Inhibitors Activate NF-{kappa}B in Human Leukemia Cells through an ATM/NEMO-related Pathway [Signal Transduction]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mechanisms underlying histone deacetylase inhibitor (HDACI)-mediated NF-B activation were investigated in human leukemia cells. Exposure of U937 and other leukemia cells to LBH-589 induced reactive oxygen species (ROS) followed by single strand (XRCC1) and double strand (-H2AX) DNA breaks. Notably, LBH-589 lethality was markedly attenuated by small interfering RNA (siRNA) knockdown of the DNA damage-linked histone, H1.2. LBH-589 triggered p65/RelA activation, NF-B-dependent induction of Mn-SOD2, and ROS elimination. Interference with LBH-589-mediated NF-B activation (e.g. in IB super-repressor transfected cells) diminished...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Rosato, R. R., Kolla, S. S., Hock, S. K., Almenara, J. A., Patel, A., Amin, S., Atadja, P., Fisher, P. B., Dent, P., Grant, S. Tags: Signal Transduction Source Type: journals

Regulation of Microtubule Dynamics through Phosphorylation on Stathmin by Epstein-Barr Virus Kinase BGLF4 [Protein Synthesis and Degradation]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, we have shown that a viral Ser/Thr kinase can directly modulate the activity of stathmin and this contributes to alteration of cellular MT dynamics and then may modulate the associated cellular processes. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Chen, P.-W., Lin, S.-J., Tsai, S.-C., Lin, J.-H., Chen, M.-R., Wang, J.-T., Lee, C.-P., Tsai, C.-H. Tags: Protein Synthesis and Degradation Source Type: journals

Revelation of p53-independent Function of MTA1 in DNA Damage Response via Modulation of the p21WAF1-Proliferating Cell Nuclear Antigen Pathway [Cell Biology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although metastasis-associated protein 1 (MTA1), a component of the nucleosome remodeling and deacetylase (NuRD) complex, is a DNA-damage response protein and regulates p53-dependent DNA repair, it remains unknown whether MTA1 also participates in p53-independent DNA damage response. Here, we provide evidence that MTA1 is a p53-independent transcriptional corepressor of p21WAF1, and the underlying mechanism involves recruitment of MTA1-histone deacetylase 2 (HDAC2) complexes onto two selective regions of the p21WAF1 promoter. Accordingly, MTA1 depletion, despite its effect on p53 down-regulation, superinduces p21WAF1, incr...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Li, D.-Q., Pakala, S. B., Reddy, S. D. N., Ohshiro, K., Peng, S.-H., Lian, Y., Fu, S. W., Kumar, R. Tags: Cell Biology Source Type: journals

Pro-hormone Secretogranin II Regulates Dense Core Secretory Granule Biogenesis in Catecholaminergic Cells [Cell Biology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood. Here, we present evidence that DCG biogenesis is dependent on the secretory protein secretogranin (Sg) II, a member of the granin family of pro-hormone cargo of DCGs in neuroendocrine cells. Depletion of SgII expression in PC12 cells leads to a decrease in both the number and size of DCGs and impairs DCG trafficking of other regulated hormones. Expression of SgII fusion proteins in a secretory-deficient PC12 variant rescues a regulated secretory pathway. SgII-containing dense core vesicles share morphol...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Courel, M., Soler-Jover, A., Rodriguez-Flores, J. L., Mahata, S. K., Elias, S., Montero-Hadjadje, M., Anouar, Y., Giuly, R. J., O'Connor, D. T., Taupenot, L. Tags: Cell Biology Source Type: journals

Physical Interaction of Jab1 with Human Serotonin 6 G-protein-coupled Receptor and Their Possible Roles in Cell Survival [Signal Transduction]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The 5-HT6 receptor (5-HT6R) is one of the most recently cloned serotonin receptors, and it plays important roles in Alzheimer disease, depression, and learning and memory disorders. However, unlike the other serotonin receptors, the cellular mechanisms of 5-HT6R are poorly elucidated relative to its significance in human brain diseases. Here, using a yeast two-hybrid assay, we found that the human 5-HT6R interacts with Jun activation domain-binding protein-1 (Jab1). We also confirmed a physical interaction between 5-HT6R and Jab1 using glutathione S-transferase pulldown, fluorescence resonance energy transfer, co-immunopre...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Yun, H.-M., Baik, J.-H., Kang, I., Jin, C., Rhim, H. Tags: Signal Transduction Source Type: journals

Recessive COL6A2 C-globular Missense Mutations in Ullrich Congenital Muscular Dystrophy: ROLE OF THE C2a SPLICE VARIANT [Molecular Bases Of Disease]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ullrich congenital muscular dystrophy (UCMD) is a disabling and life-threatening disorder resulting from either recessive or dominant mutations in genes encoding collagen VI. Although the majority of the recessive UCMD cases have frameshift or nonsense mutations in COL6A1, COL6A2, or COL6A3, recessive structural mutations in the COL6A2 C-globular region are emerging also. However, the underlying molecular mechanisms have remained elusive. Here we identified a homozygous COL6A2 E624K mutation (C1 subdomain) and a homozygous COL6A2 R876S mutation (C2 subdomain) in two UCMD patients. The consequences of the mutations were inv...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Zhang, R.-Z., Zou, Y., Pan, T.-C., Markova, D., Fertala, A., Hu, Y., Squarzoni, S., Reed, U. C., Marie, S. K. N., Bonnemann, C. G., Chu, M.-L. Tags: Molecular Bases Of Disease Source Type: journals

Podocyte Injury Induces Nuclear Translocation of WTIP via Microtubule-dependent Transport [Molecular Bases Of Disease]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Podocyte structural and transcriptional phenotype plasticity characterizes glomerular injury. Transcriptional activity of WT1 (Wilm's tumor 1) is required for normal podocyte structure and is repressed by the podocyte adherens junction protein, WTIP (WT1 interacting protein). Here we show that WTIP translocated into podocyte nuclei in lipopolysaccharide (LPS)-treated mice, a model of transient nephrotic syndrome. Cultured podocytes, which stably expressed an epitope-tagged WTIP, were treated with LPS. Imaging and cellular fractionation studies demonstrated that WTIP translocated from podocyte cell contacts into nuclei with...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Kim, J. H., Konieczkowski, M., Mukherjee, A., Schechtman, S., Khan, S., Schelling, J. R., Ross, M. D., Bruggeman, L. A., Sedor, J. R. Tags: Molecular Bases Of Disease Source Type: journals

A Conformational Switch in the Scaffolding Protein NHERF1 Controls Autoinhibition and Complex Formation [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mammalian Na+/H+ exchange regulatory factor 1 (NHERF1) is a multidomain scaffolding protein essential for regulating the intracellular trafficking and macromolecular assembly of transmembrane ion channels and receptors. NHERF1 consists of tandem PDZ-1, PDZ-2 domains that interact with the cytoplasmic domains of membrane proteins and a C-terminal (CT) domain that binds the membrane-cytoskeleton linker protein ezrin. NHERF1 is held in an autoinhibited state through intramolecular interactions between PDZ2 and the CT domain that also includes a C-terminal PDZ-binding motif (-SNL). We have determined the structures of the ...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Bhattacharya, S., Dai, Z., Li, J., Baxter, S., Callaway, D. J. E., Cowburn, D., Bu, Z. Tags: Protein Structure and Folding Source Type: journals

Global Conformational Change Associated with the Two-step Reaction Catalyzed by Escherichia coli Lipoate-Protein Ligase A [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Lipoate-protein ligase A (LplA) catalyzes the attachment of lipoic acid to lipoate-dependent enzymes by a two-step reaction: first the lipoate adenylation reaction and, second, the lipoate transfer reaction. We previously determined the crystal structure of Escherichia coli LplA in its unliganded form and a binary complex with lipoic acid (Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A., and Taniguchi, H. (2005) J Biol. Chem. 280, 33645–33651). Here, we report two new LplA structures, LplA·lipoyl-5'-AMP and LplA·octyl-5'-AMP·apoH-protein complexes, which represent the post-l...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Fujiwara, K., Maita, N., Hosaka, H., Okamura-Ikeda, K., Nakagawa, A., Taniguchi, H. Tags: Protein Structure and Folding Source Type: journals

Crystal Structure of Get4-Get5 Complex and Its Interactions with Sgt2, Get3, and Ydj1 [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Get3, Get4, and Get5 in Saccharomyces cerevisiae participate in the insertion of tail-anchored proteins into the endoplasmic reticulum membrane. We elucidated the interaction between Get4 and Get5 and investigated their interaction with Get3 and a tetratricopeptide repeat-containing protein, Sgt2. Based on co-immunoprecipitation and crystallographic studies, Get4 and Get5 formed a tight complex, suggesting that they constitute subunits of a larger complex. In contrast, although Get3 interacted physically with the Get4-Get5 complex, low amounts of Get3 co-precipitated with Get5, implying a transient interaction between Get3...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Chang, Y.-W., Chuang, Y.-C., Ho, Y.-C., Cheng, M.-Y., Sun, Y.-J., Hsiao, C.-D., Wang, C. Tags: Protein Structure and Folding Source Type: journals

Hyaluronan Mixed Esters of Butyric and Retinoic Acid Affording Myocardial Survival and Repair without Stem Cell Transplantation [Glycobiology and Extracellular Matrices]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, efficient cardiac regenerative therapy can be afforded by HBR without the need of stem cell transplantation or vector-mediated gene delivery. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Lionetti, V., Cantoni, S., Cavallini, C., Bianchi, F., Valente, S., Frascari, I., Olivi, E., Aquaro, G. D., Bonavita, F., Scarlata, I., Maioli, M., Vaccari, V., Tassinari, R., Bartoli, A., Recchia, F. A., Pasquinelli, G., Ventura, C. Tags: Glycobiology and Extracellular Matrices Source Type: journals

Akt Cys-310-targeted Inhibition by Hydroxylated Benzene Derivatives Is Tightly Linked to Their Immunosuppressive Effects [Cell Biology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we characterized Akt (protein kinase B)-targeted regulation by HQ and its derivatives, in suppressing inflammatory responses using cellular, molecular, biochemical, and immunopharmacological approaches. HQ down-regulated inflammatory responses such as NO production, surface levels of pattern recognition receptors, and cytokine gene expression with IC50 values that ranged from 5 to 10 µm. HQ inhibition was mediated by blocking NF-B activation via suppression of its translocation pathway, which is composed of Akt, IB kinase β, and IB. Of the targets in this pathway, HQ directly targeted and bound to ...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Lee, J. Y., Lee, Y. G., Lee, J., Yang, K.-J., Kim, A. R., Kim, J. Y., Won, M.-H., Park, J., Yoo, B. C., Kim, S., Cho, W.-J., Cho, J. Y. Tags: Cell Biology Source Type: journals

Secretin Occupies a Single Protomer of the Homodimeric Secretin Receptor Complex: INSIGHTS FROM PHOTOAFFINITY LABELING STUDIES USING DUAL SITES OF COVALENT ATTACHMENT [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The secretin receptor, a prototypic family B G protein-coupled receptor, forms a constitutive homodimeric complex that is stable even in the presence of hormone. Recently, a model of this agonist-bound receptor was built based on high resolution structures reported for amino-terminal domains of other family members. Although this model provided the best solution for all extant data, including 10 photoaffinity labeling constraints, a new such constraint now obtained with a position 16 photolabile probe was inconsistent with this model. As the secretin receptor forms constitutive homodimers, we explored whether secretin migh...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Dong, M., Lam, P. C.-H., Pinon, D. I., Orry, A., Sexton, P. M., Abagyan, R., Miller, L. J. Tags: Protein Structure and Folding Source Type: journals

Neuropilin 1 Directly Interacts with Fer Kinase to Mediate Semaphorin 3A-induced Death of Cortical Neurons [Molecular Bases Of Disease]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Neuropilins (NRPs) are receptors for the major chemorepulsive axonal guidance cue semaphorins (Sema). The interaction of Sema3A/NRP1 during development leads to the collapse of growth cones. Here we show that Sema3A also induces death of cultured cortical neurons through NRP1. A specific NRP1 inhibitory peptide ameliorated Sema3A-evoked cortical axonal retraction and neuronal death. Moreover, Sema3A was also involved in cerebral ischemia-induced neuronal death. Expression levels of Sema3A and NRP1, but not NRP2, were significantly increased early during brain reperfusion following transient focal cerebral ischemia. NRP1 in...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Jiang, S. X., Whitehead, S., Aylsworth, A., Slinn, J., Zurakowski, B., Chan, K., Li, J., Hou, S. T. Tags: Molecular Bases Of Disease Source Type: journals

Molecular Interfaces of the Galactose-binding Protein Tectonin Domains in Host-Pathogen Interaction [Molecular Biophysics]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
β-Propeller proteins function in catalysis, protein-protein interaction, cell cycle regulation, and innate immunity. The galactose-binding protein (GBP) from the plasma of the horseshoe crab, Carcinoscorpius rotundicauda, is a β-propeller protein that functions in antimicrobial defense. Studies have shown that upon binding to Gram-negative bacterial lipopolysaccharide (LPS), GBP interacts with C-reactive protein (CRP) to form a pathogen-recognition complex, which helps to eliminate invading microbes. However, the molecular basis of interactions between GBP and LPS and how it interplays with CRP remain largely unk...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Low, D. H. P., Frecer, V., Le Saux, A., Srinivasan, G. A., Ho, B., Chen, J., Ding, J. L. Tags: Molecular Biophysics Source Type: journals

In Vitro and in Vivo Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-XL [Neurobiology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human neural stem cells derived from the ventral mesencephalon (VM) are powerful research tools and candidates for cell therapies in Parkinson disease. Previous studies with VM dopaminergic neuron (DAn) precursors indicated poor growth potential and unstable phenotypical properties. Using the model cell line hVM1 (human ventral mesencephalic neural stem cell line 1; a new human fetal VM stem cell line), we have found that Bcl-XL enhances the generation of DAn from VM human neural stem cells. Mechanistically, Bcl-XL not only exerts the expected antiapoptotic effect but also induces proneural (NGN2 and NEUROD1) and dopamine-...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Courtois, E. T., Castillo, C. G., Seiz, E. G., Ramos, M., Bueno, C., Liste, I., Martinez-Serrano, A. Tags: Neurobiology Source Type: journals

Low Density Subcellular Fractions Enhance Disease-specific Prion Protein Misfolding [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The production of prion particles in vitro by amplification with or without exogenous seed typically results in infectivity titers less than those associated with PrPSc isolated ex vivo and highlights the potential role of co-factors that can catalyze disease-specific prion protein misfolding in vivo. We used a cell-free conversion assay previously shown to replicate many aspects of transmissible spongiform encephalopathy disease to investigate the cellular location of disease-specific co-factors using fractions derived from gradient centrifugation of a scrapie-susceptible cell line. Fractions from the low density region o...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Graham, J. F., Agarwal, S., Kurian, D., Kirby, L., Pinheiro, T. J. T., Gill, A. C. Tags: Protein Structure and Folding Source Type: journals

Cul8/Rtt101 Forms a Variety of Protein Complexes That Regulate DNA Damage Response and Transcriptional Silencing [Protein Synthesis and Degradation]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The budding yeast, Saccharomyces cerevisiae, has three cullin proteins, which act as platforms for Cullin-based E3 ubiquitin ligases. Genetic evidence indicates that Cul8, together with Mms1, Mms22, and Esc4, is involved in the repair of DNA damage that can occur during DNA replication. Cul8 is thought to form a complex with these proteins, but the composition and the function of Cul8-based E3 ubiquitin ligases remain largely uncharacterized. Herein, we report a comprehensive biochemical analysis of Cul8 complexes. Cul8 was found to form a Cul8-Mms1-Mms22-Esc4 complex under physiological conditions, with Mms1 bridging Cul8...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Mimura, S., Yamaguchi, T., Ishii, S., Noro, E., Katsura, T., Obuse, C., Kamura, T. Tags: Protein Synthesis and Degradation Source Type: journals

Functional Interaction of Phosphatase and Tensin Homologue (PTEN) with the E3 Ligase NEDD4-1 during Neuronal Response to Zinc [Protein Synthesis and Degradation]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study demonstrates that NEDD4-1-mediated PTEN ubiquitination is crucial in the regulation of PI3K/Akt signaling by PTEN during the neuronal response to zinc, which may represent a common mechanism in neurodegeneration. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Kwak, Y.-D., Wang, B., Pan, W., Xu, H., Jiang, X., Liao, F.-F. Tags: Protein Synthesis and Degradation Source Type: journals

Nuclear Factor {kappa}B- and Specificity Protein 1-dependent p53-mediated Bi-directional Regulation of the Human Manganese Superoxide Dismutase Gene [Signal Transduction]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumor suppressor p53 is known to activate certain sets of genes while suppressing others. However, whether p53 can both activate and suppress the same gene is unclear. To address this question, concentration-dependent p53 effect on the manganese superoxide dismutase (MnSOD) gene was investigated. By transfecting p53 in PC-3 cells, we demonstrate that low concentrations of p53 increase while high concentrations suppress MnSOD expression. The physiological relevance of this effect was determined in vitro and in vivo using combined UVB-mediated activation and small interference RNA-mediated suppression of p53. Results were co...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Dhar, S. K., Xu, Y., St. Clair, D. K. Tags: Signal Transduction Source Type: journals

Altered Function of the SCN1A Voltage-gated Sodium Channel Leads to {gamma}-Aminobutyric Acid-ergic (GABAergic) Interneuron Abnormalities [Molecular Bases Of Disease]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Voltage-gated sodium channels are required for the initiation and propagation of action potentials. Mutations in the neuronal voltage-gated sodium channel SCN1A are associated with a growing number of disorders including generalized epilepsy with febrile seizures plus (GEFS+),7 severe myoclonic epilepsy of infancy, and familial hemiplegic migraine. To gain insight into the effect of SCN1A mutations on neuronal excitability, we introduced the human GEFS+ mutation SCN1A-R1648H into the orthologous mouse gene. Scn1aRH/RH mice homozygous for the R1648H mutation exhibit spontaneous generalized seizures and premature death betwe...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Martin, M. S., Dutt, K., Papale, L. A., Dube, C. M., Dutton, S. B., de Haan, G., Shankar, A., Tufik, S., Meisler, M. H., Baram, T. Z., Goldin, A. L., Escayg, A. Tags: Molecular Bases Of Disease Source Type: journals

CDKN1C Negatively Regulates RNA Polymerase II C-terminal Domain Phosphorylation in an E2F1-dependent Manner [Cell Biology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CDKN1C is a cyclin-dependent kinase inhibitor and is a candidate tumor suppressor gene. We previously found that the CDKN1C protein represses E2F1-driven transcription in an apparent negative feedback loop. Herein, we explore the mechanism by which CDKN1C represses transcription. We find that adenoviral-mediated overexpression of CDKN1C leads to a dramatic reduction in phosphorylation of the RNA polymerase II (pol II) C-terminal domain (CTD). RNA interference studies demonstrate that this activity is not an artifact of CDKN1C overexpression, because endogenous CDKN1C mediates an inhibition of RNA pol II CTD phosphorylation...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Ma, Y., Chen, L., Wright, G. M., Pillai, S. R., Chellappan, S. P., Cress, W. D. Tags: Cell Biology Source Type: journals

Last Step in the Conversion of Trehalose to Glycogen: A MYCOBACTERIAL ENZYME THAT TRANSFERS MALTOSE FROM MALTOSE 1-PHOSPHATE TO GLYCOGEN [Glycobiology and Extracellular Matrices]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We show that Mycobacterium smegmatis has an enzyme catalyzing transfer of maltose from [14C]maltose 1-phosphate to glycogen. This enzyme was purified 90-fold from crude extracts and characterized. Maltose transfer required addition of an acceptor. Liver, oyster, or mycobacterial glycogens were the best acceptors, whereas amylopectin had good activity, but amylose was a poor acceptor. Maltosaccharides inhibited the transfer of maltose from [14C]maltose-1-P to glycogen because they were also acceptors of maltose, and they caused production of larger sized radioactive maltosaccharides. When maltotetraose was the acceptor, ove...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Elbein, A. D., Pastuszak, I., Tackett, A. J., Wilson, T., Pan, Y. T. Tags: Glycobiology and Extracellular Matrices Source Type: journals

Anti-inflammatory Compounds Parthenolide and Bay 11-7082 Are Direct Inhibitors of the Inflammasome [Immunology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Activation of the inflammasome generates the pro-inflammatory cytokines interleukin-1β and -18, which are important mediators of inflammation. Abnormal activation of the inflammasome leads to many inflammatory diseases, including gout, silicosis, neurodegeneration, and genetically inherited periodic fever syndromes. Therefore, identification of small molecule inhibitors that target the inflammasome is an important step toward developing effective therapeutics for the treatment of inflammation. Here, we show that the herbal NF-B inhibitory compound parthenolide inhibits the activity of multiple inflammasomes in macroph...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Juliana, C., Fernandes-Alnemri, T., Wu, J., Datta, P., Solorzano, L., Yu, J.-W., Meng, R., Quong, A. A., Latz, E., Scott, C. P., Alnemri, E. S. Tags: Immunology Source Type: journals

Energy Restriction as an Antitumor Target of Thiazolidinediones [Metabolism]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cancer cells gain growth advantages in the microenvironment by shifting cellular metabolism to aerobic glycolysis, the so-called Warburg effect. There is a growing interest in targeting aerobic glycolysis for cancer therapy by exploiting the differential susceptibility of malignant versus normal cells to glycolytic inhibition, of which the proof-of-concept is provided by the in vivo efficacy of dietary caloric restriction and natural product-based energy restriction-mimetic agents (ERMAs) such as resveratrol and 2-deoxyglucose in suppressing carcinogenesis in animal models. Here, we identified thiazolidinediones as a novel...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Wei, S., Kulp, S. K., Chen, C.-S. Tags: Metabolism Source Type: journals

FKBP38 Protects Bcl-2 from Caspase-dependent Degradation [Protein Synthesis and Degradation]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cellular processes that regulate Bcl-2 at the posttranslational levels are as important as those that regulate bcl-2 synthesis. Previously we demonstrated that the suppression of FK506-binding protein 38 (FKBP38) contributes to the instability of Bcl-2 or leaves Bcl-2 unprotected from degradation in an unknown mechanism. Here, we studied the underlying molecular mechanism mediating this process. We first showed that Bcl-2 binding-defective mutants of FKBP38 fail to accumulate Bcl-2 protein. We demonstrated that the FKBP38-mediated Bcl-2 stability is specific as the levels of other anti-apoptotic proteins such as Bcl-XL...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Choi, B.-H., Feng, L., Yoon, H. S. Tags: Protein Synthesis and Degradation Source Type: journals

Structure of RecJ Exonuclease Defines Its Specificity for Single-stranded DNA [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
RecJ is a single-stranded DNA (ssDNA)-specific 5'-3' exonuclease that plays an important role in DNA repair and recombination. To elucidate how RecJ achieves its high specificity for ssDNA, we determined the entire structures of RecJ both in a ligand-free form and in a complex with Mn2+ or Mg2+ by x-ray crystallography. The entire RecJ consists of four domains that form a molecule with an O-like structure. One of two newly identified domains had structural similarities to an oligonucleotide/oligosaccharide-binding (OB) fold. The OB fold domain alone could bind to DNA, indicating that this domain is a novel member of the OB...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Wakamatsu, T., Kitamura, Y., Kotera, Y., Nakagawa, N., Kuramitsu, S., Masui, R. Tags: Protein Structure and Folding Source Type: journals

Pituitary Adenylate Cyclase-activating Polypeptide (PACAP)/PAC1HOP1 Receptor Activation Coordinates Multiple Neurotrophic Signaling Pathways: Akt ACTIVATION THROUGH PHOSPHATIDYLINOSITOL 3-KINASE {gamma} AND VESICLE ENDOCYTOSIS FOR NEURONAL SURVIVAL [Neurobiology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MAPK and Akt pathways are predominant mediators of trophic signaling for many neuronal systems. Among the vasoactive intestinal peptide/secretin/glucagon family of related peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) binding to specific PAC1 receptor isoforms can engage multiple signaling pathways and promote neuroprotection through mechanisms that are not well understood. Using a primary sympathetic neuronal system, the current studies demonstrate that PACAP activation of PAC1HOP1 receptors engages both MAPK and Akt neurotrophic pathways in an integrated program to facilitate neuronal survival afte...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: May, V., Lutz, E., MacKenzie, C., Schutz, K. C., Dozark, K., Braas, K. M. Tags: Neurobiology Source Type: journals

Tobacco Calcium-dependent Protein Kinases Are Differentially Phosphorylated in Vivo as Part of a Kinase Cascade That Regulates Stress Response [Plant Biology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In vivo phosphorylation sites of the tobacco calcium-dependent protein kinases NtCDPK2 and NtCDPK3 were determined in response to biotic or abiotic stress. Stress-inducible phosphorylation was exclusively located in the variable N termini, where both kinases were phosphorylated differentially despite 91% overall sequence identity. In NtCDPK2, serine 40 and threonine 65 were phosphorylated within 2 min after stress. Whereas Thr65 is subjected to intra-molecular in vivo autophosphorylation, Ser40 represents a target for a regulatory upstream protein kinase, and correct NtCDPK2 membrane localization is required for Ser40 phos...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Witte, C.-P., Keinath, N., Dubiella, U., Demouliere, R., Seal, A., Romeis, T. Tags: Plant Biology Source Type: journals

Mutation of Actin Tyr-53 Alters the Conformations of the DNase I-binding Loop and the Nucleotide-binding Cleft [Protein Structure and Folding]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
All but 11 of the 323 known actin sequences have Tyr at position 53, and the 11 exceptions have the conservative substitution Phe, which raises the following questions. What is the critical role(s) of Tyr-53, and, if it can be replaced by Phe, why has this happened so infrequently? We compared the properties of purified endogenous Dictyostelium actin and mutant constructs with Tyr-53 replaced by Phe, Ala, Glu, Trp, and Leu. The Y53F mutant did not differ significantly from endogenous actin in any of the properties assayed, but the Y53A and Y53E mutants differed substantially; affinity for DNase I was reduced, the rate of n...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Liu, X., Shu, S., Hong, M.-S. S., Yu, B., Korn, E. D. Tags: Protein Structure and Folding Source Type: journals

Inhibition of Lung Fluid Clearance and Epithelial Na+ Channels by Chlorine, Hypochlorous Acid, and Chloramines [Membrane Biology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We investigated the mechanisms by which chlorine (Cl2) and its reactive byproducts inhibit Na+-dependent alveolar fluid clearance (AFC) in vivo and the activity of amiloride-sensitive epithelial Na+ channels (ENaC) by measuring AFC in mice exposed to Cl2 (0–500 ppm for 30 min) and Na+ and amiloride-sensitive currents (INa and Iamil, respectively) across Xenopus oocytes expressing human -, β-, and -ENaC incubated with HOCl (1–2000 µm). Both Cl2 and HOCl-derived products decreased AFC in mice and whole cell and single channel INa in a dose-dependent manner; these effects were counteracted by serine pro...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Song, W., Wei, S., Zhou, Y., Lazrak, A., Liu, G., Londino, J. D., Squadrito, G. L., Matalon, S. Tags: Membrane Biology Source Type: journals

NF-{kappa}B Activation in Hypothalamic Pro-opiomelanocortin Neurons Is Essential in Illness- and Leptin-induced Anorexia [Neurobiology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Anorexia and weight loss are prevalent in infectious diseases. To investigate the molecular mechanisms underlying these phenomena, we established animal models of infection-associated anorexia by administrating bacterial and viral products, lipopolysaccharide (LPS) and human immunodeficiency virus-1 transactivator protein (Tat). In these models, we found that the nuclear factor-B (NF-B), a pivotal transcription factor for inflammation-related proteins, was activated in the hypothalamus. In parallel, administration of LPS and Tat increased hypothalamic pro-inflammatory cytokine production, which was abrogated by inhibition ...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Jang, P.-G., Namkoong, C., Kang, G. M., Hur, M.-W., Kim, S.-W., Kim, G. H., Kang, Y., Jeon, M.-J., Kim, E. H., Lee, M.-S., Karin, M., Baik, J.-H., Park, J.-Y., Lee, K.-U., Kim, Y.-B., Kim, M.-S. Tags: Neurobiology Source Type: journals

A Conserved Active-site Threonine Is Important for Both Sugar and Flavin Oxidations of Pyranose 2-Oxidase [Enzymology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pyranose 2-oxidase (P2O) catalyzes the oxidation by O2 of d-glucose and several aldopyranoses to yield the 2-ketoaldoses and H2O2. Based on crystal structures, in one rotamer conformation, the threonine hydroxyl of Thr169 forms H-bonds to the flavin-N5/O4 locus, whereas, in a different rotamer, it may interact with either sugar or other parts of the P2O·sugar complex. Transient kinetics of wild-type (WT) and Thr169 -> S/N/G/A replacement variants show that d-Glc binds to T169S, T169N, and WT with the same Kd (45–47 mm), and the hydride transfer rate constants (kred) are similar (15.3–9.7 s–1 at ...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Pitsawong, W., Sucharitakul, J., Prongjit, M., Tan, T.-C., Spadiut, O., Haltrich, D., Divne, C., Chaiyen, P. Tags: Enzymology Source Type: journals

The Escherichia coli PriA Helicase Specifically Recognizes Gapped DNA Substrates: EFFECT OF THE TWO NUCLEOTIDE-BINDING SITES OF THE ENZYME ON THE RECOGNITION PROCESS [Molecular Biophysics]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Energetics and specificity of interactions between the Escherichia coli PriA helicase and the gapped DNAs have been studied, using the quantitative fluorescence titration and analytical ultracentrifugation methods. The gap complex has a surprisingly low minimum total site size, corresponding to ~7 nucleotides of the single-stranded DNA (ssDNA), as compared with the site size of ~20 nucleotides of the enzyme-ssDNA complex. The dramatic difference in stoichiometries indicates that the enzyme predominantly engages the strong DNA-binding subsite in interactions with the gap and assumes a very different orientation in the gap c...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Szymanski, M. R., Jezewska, M. J., Bujalowski, W. Tags: Molecular Biophysics Source Type: journals

Importance of Membrane Structural Integrity for RPE65 Retinoid Isomerization Activity [Enzymology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Regeneration of visual chromophore in the vertebrate visual cycle involves the retinal pigment epithelium-specific protein RPE65, the key enzyme catalyzing the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol. Although RPE65 has no predicted membrane spanning domains, this protein predominantly associates with microsomal fractions isolated from bovine retinal pigment epithelium (RPE). We have re-examined the nature of RPE65 interactions with native microsomal membranes by using extraction and phase separation experiments. We observe that hydrophobic interactions are the dominant forces th...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Golczak, M., Kiser, P. D., Lodowski, D. T., Maeda, A., Palczewski, K. Tags: Enzymology Source Type: journals

A VHH That Neutralizes the Zinc Metalloproteinase Activity of Botulinum Neurotoxin Type A [Immunology]Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, a heavy chain antibody fragment (VH/VHH) phage display library was constructed by amplification of the immunoglobulin genes of a nonimmune camel, Camelus dromedarius, using primers specific to human VH gene segments. A recombinant light chain of type A botulinum toxin, BoTxA/LC, with zinc endoprotease activity was used in phage bio-panning to select phage clones displaying BoTxA/LC-bound VH/VHH. Soluble VH/VHH were produced and purified from 10 VH/VHH phagemid-transformed E. coli clones. Complementary determining regions (CDRs) and immunoglobulin frameworks (FRs) of the 10 camel VH/VHH-deduced amino acid seq...
Source: Journal of Biological Chemistry - March 19, 2010 Category: Chemistry Authors: Thanongsaksrikul, J., Srimanote, P., Maneewatch, S., Choowongkomon, K., Tapchaisri, P., Makino, S.-i., Kurazono, H., Chaicumpa, W. Tags: Immunology Source Type: journals