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| molecular chaperonesSummarySummary: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the CHAPERONINS, the HEAT-SHOCK PROTEINS 70, and the HSP90 HEAT-SHOCK PROTEINS. Top Publications
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One step at a time: endoplasmic reticulum-associated degradationShruthi S Vembar
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
Nat Rev Mol Cell Biol 9:944-57. 2008..During ERAD, molecular chaperones and associated factors recognize and target substrates for retrotranslocation to the cytoplasm, where they ..
Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and agingRichard I Morimoto
Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA
Genes Dev 22:1427-38. 2008....
HSP90 and the chaperoning of cancerLuke Whitesell
Steele Memorial Children s Research Center, University of Arizona, Tucson, Arizona 85724, USA
Nat Rev Cancer 5:761-72. 2005Standing watch over the proteome, molecular chaperones are an ancient and evolutionarily conserved class of proteins that guide the normal folding, intracellular disposition and proteolytic turnover of many of the key regulators of cell ..
HSP90 at the hub of protein homeostasis: emerging mechanistic insightsMikko Taipale
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Rev Mol Cell Biol 11:515-28. 2010..Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions...
Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiologyM E Feder
Department of Organismal Biology and Anatomy and Committee on Evolutionary Biology, University of Chicago, Illinois 60637, USA
Annu Rev Physiol 61:243-82. 1999b>Molecular chaperones, including the heat-shock proteins (Hsps), are a ubiquitous feature of cells in which these proteins cope with stress-induced denaturation of other proteins...
Converging concepts of protein folding in vitro and in vivoF Ulrich Hartl
Max Planck Institute of Biochemistry, Department of Cellular Biochemistry, Martinsried, Germany
Nat Struct Mol Biol 16:574-81. 2009..with a focus on how proteins navigate the complex folding energy landscape inside cells with the aid of molecular chaperones. Understanding these reactions is also of considerable medical relevance, as the aggregation of misfolding ..
ER chaperones in mammalian development and human diseasesMin Ni
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Ave, Los Angeles, CA 90089 9176, United States
FEBS Lett 581:3641-51. 2007....
Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagyAna Maria Cuervo
Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Science 305:1292-5. 2004..These findings may underlie the toxic gain-of-function by the mutants...
Biological and chemical approaches to diseases of proteostasis deficiencyEvan T Powers
Departments of Chemistry and Molecular and Experimental Medicine and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Annu Rev Biochem 78:959-91. 2009..We propose that such therapeutic strategies, including combination therapies, represent a new approach for treating a range of diverse human maladies...
Hsp70 chaperones: cellular functions and molecular mechanismM P Mayer
Zentrum für Molekulare Biologie ZMBH, Universitat Heidelberg, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany
Cell Mol Life Sci 62:670-84. 2005Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts...
Molecular chaperones in protein folding and proteostasisF Ulrich Hartl
Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
Nature 475:324-32. 2011..To avoid these dangers, cells invest in a complex network of molecular chaperones, which use ingenious mechanisms to prevent aggregation and promote efficient folding...
CBP/p300-mediated acetylation of histone H3 on lysine 56Chandrima Das
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, PO Box 6511, Aurora Colorado 80045, USA
Nature 459:113-7. 2009....
Dynamic interaction of BiP and ER stress transducers in the unfolded-protein responseA Bertolotti
Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA
Nat Cell Biol 2:326-32. 2000..These findings are consistent with a model in which BiP represses signalling through PERK and IRE1 and protein misfolding relieves this repression by effecting the release of BiP from the PERK and IRE1 lumenal domains...
Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelopeRose E Goodchild
Department of Neurology, Columbia University, New York, New York 10032, USA
Neuron 48:923-32. 2005..These observations demonstrate that neurons have a unique requirement for nuclear envelope localized torsinA function and suggest that loss of this activity is a key molecular event in the pathogenesis of DYT1 dystonia...
Guidelines for the nomenclature of the human heat shock proteinsHarm H Kampinga
Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Cell Stress Chaperones 14:105-11. 2009..In addition to this nomenclature, we provide a list of the human Entrez Gene IDs and the corresponding Entrez Gene IDs for the mouse orthologs...
RNA chaperones, RNA annealers and RNA helicasesLukas Rajkowitsch
Max F Perutz Laboratories, University of Vienna, Vienna, Austria
RNA Biol 4:118-30. 2007..Finally, we present a new website for proteins with RNA chaperone activity which compiles all the information on these proteins with the perspective to promote the understanding of their activity...
BAG-6 is essential for selective elimination of defective proteasomal substratesRyosuke Minami
Department of Biological Sciences, Tokyo Metropolitan University, Tokyo, Japan
J Cell Biol 190:637-50. 2010..Therefore, we propose that BAG-6 is necessary for ubiquitin-mediated degradation of newly synthesized defective polypeptides...
The mitochondrial UPR - protecting organelle protein homeostasisCole M Haynes
Cell Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 390, New York, NY 10065, USA
J Cell Sci 123:3849-55. 2010..Mitochondria have dedicated molecular chaperones and proteases that promote proper protein folding, complex assembly and quality control...
Regulated translation initiation controls stress-induced gene expression in mammalian cellsH P Harding
Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
Mol Cell 6:1099-108. 2000..Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals...
A ribosome-associating factor chaperones tail-anchored membrane proteinsMalaiyalam Mariappan
Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 466:1120-4. 2010..Thus, the Bat3 complex acts as a TMD-selective chaperone that effectively channels TA proteins to the TRC40 insertion pathway...
A molecular mechanism underlying the neural-specific defect in torsinA mutant miceConnie E Kim
Department of Neurology and Integrated Graduate Program in Cellular, Molecular, Structural, and Genetic Studies, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 107:9861-6. 2010....
Primary dystonia: molecules and mechanismsLauren M Tanabe
Department of Pharmacology, Columbia University, New York, NY, USA
Nat Rev Neurol 5:598-609. 2009..Other dystonia-related gene products traffic through the endoplasmic reticulum, suggesting a potential cell biological theme underlying primary dystonia...
Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cellsTereza Vogiatzi
Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Soranou Efesiou 4, Athens, Greece
J Biol Chem 283:23542-56. 2008..These results indicate that CMA and macroautophagy are important pathways for WT ASYN degradation in neurons and underline the importance of CMA as degradation machinery in the nervous system...
Structural biology of the chaperone-usher pathway of pilus biogenesisGabriel Waksman
Institute of Structural and Molecular Biology, University College London and Birkbeck College, Malet Street, London, UK
Nat Rev Microbiol 7:765-74. 2009..Other studies have provided the molecular basis of host recognition by CU pili. The knowledge that has been gathered about both the assembly of and host recognition by CU pili has been harnessed to design promising antibiotic compounds...
The unfolded protein response: a stress signaling pathway critical for health and diseaseKezhong Zhang
Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Neurology 66:S102-9. 2006..This review summarizes the complex regulation of UPR signaling and its relevance to human physiology and disease...
Growth phase-dependent variation in protein composition of the Escherichia coli nucleoidT Ali Azam
Department of Molecular Genetics, National Institute of Genetics, Mishima, Shizuoka 411 8540, Japan
J Bacteriol 181:6361-70. 1999..These changes in the composition of nucleoid-associated proteins in the stationary phase are accompanied by compaction of the genome DNA and silencing of the genome functions...
Activation of the DNA damage checkpoint in yeast lacking the histone chaperone anti-silencing function 1Christopher Josh Ramey
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center at Fitzsimons, P O Box 6511, Aurora, CO 80045, USA
Mol Cell Biol 24:10313-27. 2004....
Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagyMarta Martinez-Vicente
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, New York, New York 10461, USA
J Clin Invest 118:777-88. 2008..As blockage of CMA increases cellular vulnerability to stressors, we propose that dopamine-induced autophagic inhibition could explain the selective degeneration of PD dopaminergic neurons...
Protein delivery into eukaryotic cells by type III secretion machinesJorge E Galan
Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut 0636, USA
Nature 444:567-73. 2006..The study of these systems is leading to unique insights into not only organelle assembly and protein secretion but also mechanisms of symbiosis and pathogenesis...
The mammalian unfolded protein responseMartin Schroder
School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, United Kingdom
Annu Rev Biochem 74:739-89. 2005..Finally, we summarize data that demonstrate that UPR signaling feeds into decision making in other processes previously thought to be unrelated to ER function, e.g., eukaryotic starvation responses and differentiation programs...
Quaternary dynamics and plasticity underlie small heat shock protein chaperone functionFlorian Stengel
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom
Proc Natl Acad Sci U S A 107:2007-12. 2010Small Heat Shock Proteins (sHSPs) are a diverse family of molecular chaperones that prevent protein aggregation by binding clients destabilized during cellular stress...
GRP78 induction in cancer: therapeutic and prognostic implicationsAmy S Lee
Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
Cancer Res 67:3496-9. 2007..Furthermore, the recent discovery of GRP78 on the cell surface of cancer cells but not in normal tissues suggests that targeted therapy against cancer via surface GRP78 may be feasible...
Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machineryWilliam B Pratt
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0632, USA
Exp Biol Med (Maywood) 228:111-33. 2003..This purified system should facilitate understanding of how eukaryotic hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction...
Nucleic acid chaperone activity of the ORF1 protein from the mouse LINE-1 retrotransposonS L Martin
Department of Cellular and Structural Biology, University of Colorado School of Medicine, Denver, Colorado 80262, USA
Mol Cell Biol 21:467-75. 2001..These findings suggest a role for L1 ORF1p in mediating nucleic acid strand transfer steps during L1 reverse transcription...
Structural basis for the regulated protease and chaperone function of DegPTobias Krojer
Research Institute for Molecular Pathology IMP, Dr Bohrgasse 7, A 1030 Vienna, Austria
Nature 453:885-90. 2008..Oligomer reassembly and concomitant activation on substrate binding may also be critical in regulating other HtrA proteases implicated in protein-folding diseases...
AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradationEfrat Rabinovich
Department of Biochemistry, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
Mol Cell Biol 22:626-34. 2002..responsible for import of nascent proteins, this bidirectional passage should be coordinated, probably by molecular chaperones. Here we implicate the cytosolic chaperone AAA-ATPase p97/Cdc48p in ERAD...
Caught with their PAMPs down? The extracellular signalling actions of molecular chaperones are not due to microbial contaminantsBrian Henderson
UCL Eastman Dental Institute, University College London, UK
Cell Stress Chaperones 15:123-41. 2010..years, it has been hypothesised that a new signalling system may exist in vertebrates in which secreted molecular chaperones form a dynamic continuum between the cellular stress response and corresponding homeostatic physiological ..
Altered responses to dopaminergic D2 receptor activation and N-type calcium currents in striatal cholinergic interneurons in a mouse model of DYT1 dystoniaA Pisani
Clinica Neurologica, Dipartimento di Neuroscienze, Universita Tor Vergata, Rome, Italy, and Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
Neurobiol Dis 24:318-25. 2006..Our data support the existence of an imbalance between striatal dopaminergic and cholinergic signaling in DYT1 dystonia...
Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targetsAndré Patrick Arrigo
Laboratoire Stress, Chaperons et Mort Cellulaire, CNRS, UMR5534, Centre de Genetique Moleculaire et Cellulaire, Universite Lyon 1, Bat Gregor Mendel, 16 rue Dubois, F 69622, Villeurbanne Cedex, France
FEBS Lett 581:3665-74. 2007Hsp27 and alphaB-crystallin are molecular chaperones that are constitutively expressed in several mammalian cells, particularly in pathological conditions...
Bat3 promotes the membrane integration of tail-anchored proteinsPawel Leznicki
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
J Cell Sci 123:2170-8. 2010....
A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cellsHiroki Nagai
Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, Room 354b, 295 Congress Avenue, New Haven, CT 06511, USA
Proc Natl Acad Sci U S A 102:826-31. 2005..Thus, Legionella has the ability to engage synthesized substrate proteins and transfer them into host cells on contact, enabling Legionella to rapidly alter transport of the vacuole in which it resides...
Heat-shock protein 90, a chaperone for folding and regulationD Picard
Cell Mol Life Sci 59:1640-8. 2002..The large conformational flexibility of Hsp90 and a multitude of dynamic co-chaperone complexes contribute to generating functional diversity, and allow Hsp90 to assist a wide range of substrates...
Heat shock proteins in cancer: chaperones of tumorigenesisStuart K Calderwood
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Trends Biochem Sci 31:164-72. 2006....
Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalphaMeelad M Dawlaty
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Cell 133:103-15. 2008..Furthermore, mice with low amounts of RanBP2 are highly sensitive to tumor formation. Together, these data identify RanBP2 as a chromosomal instability gene that regulates Topo IIalpha by sumoylation and suppresses tumorigenesis...
Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1Anne Rufiange
Centre de recherche en cancérologie de l Université Laval, L Hôtel Dieu de Québec CHUQ, Quebec, Canada
Mol Cell 27:393-405. 2007..Taken together, our data underline the dynamic nature of replication-independent nucleosome assembly/disassembly, specify a link to transcription, and implicate Asf1 and H3 K56 acetylation...
Asf1 mediates histone eviction and deposition during elongation by RNA polymerase IIMarc A Schwabish
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 22:415-22. 2006..Lastly, Asf1 inhibits internal initiation from cryptic promoters within coding regions. These results strongly suggest that Asf1 functions as an elongation factor to disassemble and reassemble histones during Pol II elongation...
Human Asf1 regulates the flow of S phase histones during replicational stressAnja Groth
Institute of Cancer Biology, The Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
Mol Cell 17:301-11. 2005....
Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cellsElke Pogge von Strandmann
Department of Internal Medicine I, University Hospital of Cologne, Kerpener Str 62, D 50924 Cologne, Germany
Immunity 27:965-74. 2007..We propose a concept for target cell recognition by NK cells beyond "missing self" and "induced self," mediated through a tumor cell-derived extracellular factor...
The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding proteinL J Ozelius
Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, USA
Nat Genet 17:40-8. 1997..This protein has homologues in nematode, rat, mouse and humans, with some resemblance to the family of heat-shock proteins and Clp proteases...
Cell cycle- and chaperone-mediated regulation of H3K56ac incorporation in yeastTommy Kaplan
School of Computer Science and Engineering, The Hebrew University, Jerusalem, Israel
PLoS Genet 4:e1000270. 2008....
Histone H3-K56 acetylation is catalyzed by histone chaperone-dependent complexesToshiaki Tsubota
Program in Gene Function and Expression, University of Massachusetts Medical School, 364 Plantation Street 506, Worcester, MA 01605, USA
Mol Cell 25:703-12. 2007..Additionally, these complexes are functionally distinct, with the Rtt109/Asf1 complex, but not the Rtt109/Vps75 complex, being critical for resistance to genotoxic agents...
Regulation of replication fork progression through histone supply and demandAnja Groth
Laboratory of Nuclear Dynamics and Genome Plasticity, UMR218 CNRS Institut Curie, 26 Rue d Ulm, 75248 Paris Cedex 05, France
Science 318:1928-31. 2007....
Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosisJ Recht
Laboratory of Chromatin Biology, The Rockefeller University, New York, NY 10021, USA
Proc Natl Acad Sci U S A 103:6988-93. 2006..In contrast, multiple asf1 mutants that are resistant to DNA damage display WT levels of K56ac. These data suggest that maintenance of H3 K56 acetylation is a primary contribution of Asf1 to genome stability in yeast...
Crystal structure of DegP (HtrA) reveals a new protease-chaperone machineTobias Krojer
Max Planck Institut fur Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, 82152 Martinsried, Germany
Nature 416:455-9. 2002b>Molecular chaperones and proteases monitor the folded state of other proteins...
Understanding the functional interplay between mammalian mitochondrial Hsp70 chaperone machine componentsArvind Vittal Goswami
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India
J Biol Chem 285:19472-82. 2010..Additionally, we highlight the biochemical defects of the mtHsp70 mutant (G489E) associated with a myelodysplastic syndrome...
The shock of aging: molecular chaperones and the heat shock response in longevity and aging--a mini-reviewStuart K Calderwood
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Gerontology 55:550-8. 2009..However, the precise mechanisms that determine the rates of aging in organisms are not known...
Cerebellothalamocortical connectivity regulates penetrance in dystoniaMiklos Argyelan
Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York 11030, USA
J Neurosci 29:9740-7. 2009..Overall, these findings point to a novel mechanism to explain differences in clinical expression in carriers of genes for brain disease...
Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109Jeffrey Fillingham
Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research CCBR, University of Toronto, 160 College St, Toronto, Ontario M5S 3E1, Canada
Mol Cell Biol 28:4342-53. 2008..Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56...
Function of dopamine transporter is compromised in DYT1 transgenic animal model in vivoJeff Hewett
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02129, USA
J Neurochem 113:228-35. 2010..These data implies that altered DAT function may contribute to impaired DA neurotransmission and clinical symptoms in human DYT1 dystonia...
Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminaseMaria Borrell-Pages
Institut Curie, CNRS UMR 146, Orsay, France
J Clin Invest 116:1410-24. 2006..Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy...
Heat shock response modulators as therapeutic tools for diseases of protein conformationSandy D Westerheide
Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA
J Biol Chem 280:33097-100. 2005..of components of the cellular quality control machinery, specifically the levels and activities of molecular chaperones, suppress aggregation and toxicity phenotypes to allow cellular function to be restored...
Commentary: Dopaminergic dysfunction in DYT1 dystoniaThomas Wichmann
Department of Neurology School of Medicine and Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA
Exp Neurol 212:242-6. 2008....
Impaired striatal D2 receptor function leads to enhanced GABA transmission in a mouse model of DYT1 dystoniaGiuseppe Sciamanna
Department of Neuroscience, University Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Neurobiol Dis 34:133-45. 2009..Our findings demonstrate a disinhibition of striatal GABAergic synaptic activity, that can be at least partially attributed to a D2 DA receptor dysfunction...
Asf1 can promote trimethylation of H3 K36 by Set2Ling Ju Lin
Department of Biochemistry, University of Alberta, MSB 5 76, Edmonton, Alberta, Canada T6G 2H7
Mol Cell Biol 30:1116-29. 2010..This function of Asf1 promotes the switch from di- to trimethylation of H3 K36 at that gene. These results support the view that Set2 function in chromatin metabolism can intimately involve histone chaperone Asf1...
Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assemblyQing Li
Department of Biochemistry and Molecular Biology, Mayo Clinic, College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
Cell 134:244-55. 2008..These results reveal a mechanism by which H3K56Ac regulates replication-coupled nucleosome assembly mediated by CAF-1 and Rtt106...
Involvement of the ubiquitin-proteasome pathway and molecular chaperones in oculopharyngeal muscular dystrophyAida Abu-Baker
Center for Research in Neuroscience, McGill University, and the McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada
Hum Mol Genet 12:2609-23. 2003..Moreover, overexpression of molecular chaperones (HSP40 and HSP70) suppressed protein aggregation and toxicity...
More than folding: localized functions of cytosolic chaperonesJason C Young
Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, D 82152, Martinsried, Germany
Trends Biochem Sci 28:541-7. 2003..Such flexibility is unique to the cytosolic Hsp70 and Hsp90 chaperone system...
Spontaneous release of cytosolic proteins from posttranslational substrates before their transport into the endoplasmic reticulumK Plath
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Cell Biol 151:167-78. 2000..Once bound to the Sec complex, the substrate is stripped of all cytosolic proteins, allowing it to subsequently be transported through the membrane channel without the interference of cytosolic binding partners...
Structural basis for the histone chaperone activity of Asf1Christine M English
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, CO 80045, USA
Cell 127:495-508. 2006..The Asf1-H3/H4 structure suggests a "strand-capture" mechanism whereby the H4 tail acts as a lever to facilitate chromatin disassembly/assembly that may be used ubiquitously by histone chaperones...
Structural insight into the regulatory mechanisms of interactions of the flagellar type III chaperone FliT with its binding partnersKatsumi Imada
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565 0871, Japan
Proc Natl Acad Sci U S A 107:8812-7. 2010....
Critical role of the stress chaperone GRP78/BiP in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor developmentDezheng Dong
Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California 90089 9176, USA
Cancer Res 68:498-505. 2008....
Effect of torsinA on membrane proteins reveals a loss of function and a dominant-negative phenotype of the dystonia-associated DeltaE-torsinA mutantGonzalo E Torres
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
Proc Natl Acad Sci U S A 101:15650-5. 2004..These properties may contribute to the autosomal dominant nature of the condition...
Abnormal motor function and dopamine neurotransmission in DYT1 DeltaGAG transgenic miceYu Zhao
University of Tennessee Health Science Center, Department of Neurology, 855 Monroe Avenue, Link Building, Suite 415, Memphis, Tennessee 38163, USA
Exp Neurol 210:719-30. 2008..Increased striatal dopamine turnover in hMT1 mice suggests that the nigrostriatal pathway may be a site of functional neuropathology in DYT1 dystonia...
Stimulation of the weak ATPase activity of human hsp90 by a client proteinStephen H McLaughlin
Cambridge University Chemical Laboratory, Lensfield Road, Cambridge, CB2 1EW, UK
J Mol Biol 315:787-98. 2002..We suggest that the tight regulation of the ATPase activity of Hsp90 is important and allows the client protein to remain bound to Hsp90 for sufficient time for activation to occur...
Knockdown and overexpression of Unc-45b result in defective myofibril organization in skeletal muscles of zebrafish embryosElena P Bernick
University of Maryland School of Medicine Interdisciplinary Training Program in Muscle Biology, Baltimore, MD 21201, USA
BMC Cell Biol 11:70. 2010..The effects of unc-45b knockdown on other sarcomeric structures and the phenotype of Unc-45b overexpression, however, are poorly understood in vertebrates...
The histone chaperone Asf1 increases the rate of histone eviction at the yeast PHO5 and PHO8 promotersPhilipp Korber
Adolf Butenandt Institut, Universitat Munchen, Schillerstrasse 44, 80336 Munich, Germany
J Biol Chem 281:5539-45. 2006..e. they both contribute toward the same outcome without being mutually strictly dependent...
Dopamine D2 receptor dysfunction is rescued by adenosine A2A receptor antagonism in a model of DYT1 dystoniaFrancesco Napolitano
CEINGE Biotecnologie Avanzate, Naples, Italy
Neurobiol Dis 38:434-45. 2010....
Dystonia-associated mutations cause premature degradation of torsinA protein and cell-type-specific mislocalization to the nuclear envelopeLisa M Giles
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322 3090, USA
Hum Mol Genet 17:2712-22. 2008....
Facilitated oligomerization of mycobacterial GroEL: evidence for phosphorylation-mediated oligomerizationC M Santosh Kumar
Laboratory of Structural Biology, Hyderabad 500001, India
J Bacteriol 191:6525-38. 2009..However, recombinant GroELs of Mycobacterium tuberculosis are unable to act as effective molecular chaperones when expressed in Escherichia coli. We demonstrate here that the inability of M...
Functions and pathologies of BiP and its interaction partnersJ Dudek
Medical Biochemistry and Molecular Biology, Saarland University, 66421, Homburg, Germany
Cell Mol Life Sci 66:1556-69. 2009..This review summarizes the physiological and pathophysiological characteristics of BiP and its interaction partners...
Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is completeJung Ae Kim
Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA 02454 9110, USA
Proc Natl Acad Sci U S A 106:1151-6. 2009..We suggest that CAF-1 and Asf1 function redundantly to deactivate the checkpoint by restoring chromatin structure on the completion of DSB repair...
RNA chaperone activity of translation initiation factor IF1Victor Croitoru
Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm, Sweden
Biochimie 88:1875-82. 2006..It is suggested that the RNA chaperone activity of IF1 contributes to RNA rearrangements during the early phase of translation initiation...
RNA chaperone activity of L1 ribosomal proteins: phylogenetic conservation and splicing inhibitionStefan L Ameres
Max F Perutz Laboratories, Department of Biochemistry, University of Vienna, Dr Bohrgasse 9 5, A 1030 Vienna, Austria
Nucleic Acids Res 35:3752-63. 2007..Mutational analysis of MjaL1 excludes the possibility that the inhibitory effect is due to stronger RNA binding. To our knowledge, MjaL1 is the first example of a protein that inhibits group I intron splicing...
Cold shock domain proteins and glycine-rich RNA-binding proteins from Arabidopsis thaliana can promote the cold adaptation process in Escherichia coliJin Sun Kim
Department of Plant Biotechnology, Agricultural Plant Stress Research Center and Biotechnology Research Institute, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 500 757, Republic of Korea
Nucleic Acids Res 35:506-16. 2007..Together, these results indicate that CSDPs and GRPs help E.coli grow and survive better during cold shock, and strongly imply that CSDP1 and GRP7 exhibit RNA chaperone activity during the cold adaptation process...
Impairment of bidirectional synaptic plasticity in the striatum of a mouse model of DYT1 dystonia: role of endogenous acetylcholineGiuseppina Martella
Department of Neuroscience, University Tor Vergata, 00133 Rome, Italy
Brain 132:2336-49. 2009..More importantly, our results indicate that an unbalanced cholinergic transmission plays a pivotal role in these alterations, providing a clue to understand the ability of anticholinergic agents to restore motor deficits in dystonia...
E. coli transports aggregated proteins to the poles by a specific and energy-dependent processAssaf Rokney
Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University, Jerusalem, Israel
J Mol Biol 392:589-601. 2009..Moreover, the results show that the processing of aggregated proteins by the protein quality control system is a multi-step process with distinct spatial and temporal controls...
pH sensing by intracellular Salmonella induces effector translocationXiu jun Yu
Section of Microbiology, Centre for Molecular Microbiology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK
Science 328:1040-3. 2010..Thus, intravacuolar Salmonella senses host cytosolic pH, resulting in the degradation of regulatory complex proteins and effector translocation...
Binding of p23 and hsp90 during assembly with the progesterone receptorJ L Johnson
Department of Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, Minnesota 55905, USA
Mol Endocrinol 9:670-8. 1995..A model is presented to relate these findings to previous models and another complex between hsp90, hsp70, and p60 that appears to be an intermediate in PR assembly...
Chaperone regulation of the heat shock protein responseRichard Voellmy
HSF Pharmaceuticals SA, Avenue des Cerisiers 39B, 1009 Pully, Switzerland
Adv Exp Med Biol 594:89-99. 2007..CHIP can activate HSF1 to regulate the protein quality control system that balances protection and degradation of chaperone substrates...
Identification by mutational analysis of amino acid residues essential in the chaperone function of calreticulinVirginie Martin
Membrane Protein Research Group and the Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
J Biol Chem 281:2338-46. 2006..This indicates that binding of ERp57 to calreticulin may not be critical for the chaperone function of calreticulin with respect to the bradykinin receptor...
Delineation of the lectin site of the molecular chaperone calreticulinSten P Thomson
Department of Biochemistry, Medical Sciences Building, University of Toronto, Toronto, ON, Canada
Cell Stress Chaperones 10:242-51. 2005..This provides the first direct demonstration of the importance of CRT's lectin site in suppressing the aggregation of nonnative glycoproteins...
The small heat shock protein IbpA of Escherichia coli cooperates with IbpB in stabilization of thermally aggregated proteins in a disaggregation competent stateMarlena Matuszewska
Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology, University of Gdansk, 80 822 Gdansk, Kladki 24, Poland
J Biol Chem 280:12292-8. 2005..IbpA and IbpB form mixed complexes, and IbpA stimulates association of IbpB with substrate...
Stable binding of ATF6 to BiP in the endoplasmic reticulum stress responseJingshi Shen
Department of Biological Sciences, Columbia University, Fairchild 813B, MC 2420, 1212 Amsterdam Avenue, New York, NY 10027, USA
Mol Cell Biol 25:921-32. 2005..We propose that stable BiP binding is essential for ATF6 regulation and that ER stress dissociates BiP from ATF6 by actively restarting the BiP ATPase cycle...
Cysteines in CH1 underlie retention of unassembled Ig heavy chainsYechiel Elkabetz
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel
J Biol Chem 280:14402-12. 2005..We propose that the role of C(H)1 cysteines in immunoglobulin assembly and secretion is not simply to engage in disulfide bridges, but to direct proper folding and interact with the retention machinery...
Wrapping the alpha-crystallin domain fold in a chaperone assemblyRobin Stamler
Department of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK
J Mol Biol 353:68-79. 2005..Together with the two previously solved structures, a total of four alpha-crystallin domain structures are now available, giving a better definition of domain boundaries for sHsps...
Evidence for an essential function of the N terminus of a small heat shock protein in vivo, independent of in vitro chaperone activityKim C Giese
Department of Biochemistry and Molecular Biophysics, University of Arizona, Tucson, AZ 85721, USA
Proc Natl Acad Sci U S A 102:18896-901. 2005....
ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ERRyo Ushioda
Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
Science 321:569-72. 2008..Thus, ERdj5 is a member of a supramolecular ERAD complex that recognizes and unfolds misfolded proteins for their efficient retrotranslocation...
Conserved residues in the N-domain of the AAA+ chaperone ClpA regulate substrate recognition and unfoldingAnnette H Erbse
Zentrum für Molekulare Biologie Heidelberg, Universitat Heidelberg, Heidelberg, Germany
FEBS J 275:1400-10. 2008..Taken together, these data suggest that ClpA utilizes two structural elements, one in the N-domain and the other in the pore of the hexamer, both of which are required for efficient unfolding of some protein substrates...
Defective protein folding and intracellular retention of thyroglobulin-R19K mutant as a cause of human congenital goiterPaul S Kim
Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Mol Endocrinol 22:477-84. 2008..Before its degradation, the Tg-R19K mutant exhibited abnormally increased association with molecular chaperones BiP, calnexin, and protein disulfide isomerase, and was unable to undergo anterograde advance from the ..
A gram-negative characteristic segment in Escherichia coli DnaK is essential for the ATP-dependent cooperative function with the co-chaperones DnaJ and GrpEShinya Sugimoto
Laboratory of Microbial Technology, Division of Microbial Science and Technology, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Hakozaki, Fukuoka, Japan
FEBS Lett 581:2993-9. 2007..Consequently, we suggest evolutionary significance for this DnaK ATPase domain segment in gram-negative bacteria towards the DnaK chaperone system...
Regulated association of misfolded endoplasmic reticulum lumenal proteins with P58/DNAJc3Kseniya Petrova
Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
EMBO J 27:2862-72. 2008..These findings are consistent with a model whereby localized activation of the Hsp70-type partner is sufficient to promote substrate handover from the J-domain co-chaperone...
Research Grants
- Role of heat shock protein 90 in alcoholic liver diseasePranoti Mandrekar; Fiscal Year: 2010..Heat shock proteins are induced by oxidative stress and function as molecular chaperones. Heat shock protein 90 (hsp90) and Grp94/gp96 chaperone signaling molecules of the TLR4 pathway to regulate ..
- MODIFICATION OF ALPHA-CRYSTALLIN CHAPERONE FUNCTIONEDATHARA ABRAHAM; Fiscal Year: 2003..We will test the hypothesis that posttranslational modifications affect the chaperone-target protein binding leading to reduced chaperone function. ..
- Role of Heat Shock Transcription Factor Hsf1 in TumorigenesisNahid F Mivechi; Fiscal Year: 2010..hallmark in the pathogenesis of cancer is the increased expression of heat shock proteins (Hsps) and other molecular chaperones. This has been observed in many human tumor types, and is considered to be an adaptive response to enhance ..
- Role of Heat Shock Transcription Factor Hsf1 in TumorigenesisNAHID MIVECHI; Fiscal Year: 2009..hallmark in the pathogenesis of cancer is the increased expression of heat shock proteins (Hsps) and other molecular chaperones. This has been observed in many human tumor types, and is considered to be an adaptive response to enhance ..
- Genetic Basis of Non-Familial IgA NephropathyTongzhong Ju; Fiscal Year: 2009....
- Genetic Basis of Non-Familial IgA NephropathyTongzhong Ju; Fiscal Year: 2010....
- Celestrols for Treatment of Neurodegenerative DiseasesRichard Silverman; Fiscal Year: 2007The expression of molecular chaperones has been shown to suppress protein misfolding/aggregation and cellular toxicity phenotypes in model systems associated with Huntington's Disease, Alzheimer's Disease, Parkinson's Disease, and ALS...
- Relative Roles of HSP70 and HSP25 in the Modulation of Renal InjuryRajasree Sreedharan; Fiscal Year: 2007..The current proposal focuses on two well recognized classes of stress inducible molecular chaperones, heat shock protein 70 and heat shock protein 25 (HSP70 and HSP25) and their function in modulating renal ..
- DEVELOPMENT AND MAINTENANCE OF LENS TRANSPARENCYJOHN IRWIN CLARK; Fiscal Year: 2010..The lens is used for these studies because of its unique accessibility for the in vivo investigation of protein unfolding and aggregation diseases in aging and the well known protective effects of ?B crystallin. ..
- DEVELOPMENT AND MAINTENANCE OF LENS TRANSPARENCYJohn Clark; Fiscal Year: 2009..The lens is used for these studies because of its unique accessibility for the in vivo investigation of protein unfolding and aggregation diseases in aging and the well known protective effects of ?B crystallin. ..
- Assembly and Trafficking of Heterotrimeric G Proteins in Vertebrate PhotoreceptorMaxim Sokolov; Fiscal Year: 2009Our long-term research objective is to understand the roles of molecular chaperones in vertebrate photoreceptors...
- Assembly and Trafficking of Heterotrimeric G Proteins in Vertebrate PhotoreceptorMaxim Sokolov; Fiscal Year: 2010Our long-term research objective is to understand the roles of molecular chaperones in vertebrate photoreceptors...
- Diabetic retinopathy: sigma receptor 1 (??R1) as a novel therapeutic target.Sylvia B Smith; Fiscal Year: 2010..The proposed project will extend these findings to understand the mechanism of this protection with the ultimate goal of determining whether (+)- pentazocine may be useful clinically for retinopathy in humans. ..
- INTRACELLULAR MECHANISMS OF GLUCOCORTICOID ACTIONDONALD BENEDICT DEFRANCO; Fiscal Year: 2010..a novel in situ fluorescence recovery after photobleaching (FRAP) assay that led to the identification of molecular chaperones and their associated co-chaperones as nuclear mobility factors for the glucocorticoid receptor (GR)...
- INTRACELLULAR MECHANISMS OF GLUCOCORTICOID ACTIONDONALD BENEDICT DEFRANCO; Fiscal Year: 2010..a novel in situ fluorescence recovery after photobleaching (FRAP) assay that led to the identification of molecular chaperones and their associated co-chaperones as nuclear mobility factors for the glucocorticoid receptor (GR)...
- Molecular Basis for Lens TransparencyHassane McHaourab; Fiscal Year: 2009..The development of a mechanistic perspective on these molecular transformations is of fundamental biochemical importance and may well have an impact on the development of intervention and therapeutic strategies. ..
- CHAPERONES AND PROTEIN BIOSYNTHESIS IN MYELOID CELLSWILLIAM NAUSEEF; Fiscal Year: 2000..we speculated that: (1) heme insertion may be a rate-limiting step in the biosynthesis of MPO and (2) molecular chaperones may interact with MPO precursors and facilitate folding events necessary for insertion of heme into heme-..
- Heat shock protein 90 antagonist-based therapy of mantle cell lymphomaKapil Bhalla; Fiscal Year: 2009..This strategy involves combinations of treatments with heat shock protein 90 and proteosome inhibitors designed to target protein folding and degradation in MCL cells. ..
- Heat shock protein 90 antagonist-based therapy of mantle cell lymphomaKapil Bhalla; Fiscal Year: 2010..This strategy involves combinations of treatments with heat shock protein 90 and proteosome inhibitors designed to target protein folding and degradation in MCL cells. ..
- Strucutre of the UNC-45 Chaperone and its Interaction with Skeletal Muscle MyosinSanford I Bernstein; Fiscal Year: 2010..b>Molecular chaperones play key roles in muscle development and function by aiding protein folding and inhibiting protein ..
- Hsp90 Regulates EphA2 Signaling and Cell Migration in GlioblastomaJennifer S Isaacs; Fiscal Year: 2010..Our studies will potentially lead to rational molecular-targeted therapeutic approaches to improve GBM survival. ..
- Strucutre of the UNC-45 Chaperone and its Interaction with Skeletal Muscle MyosinSanford I Bernstein; Fiscal Year: 2010..b>Molecular chaperones play key roles in muscle development and function by aiding protein folding and inhibiting protein ..
- Molecular/Chemistry Chaperones and HemoglobinopathiesWilliam Welch; Fiscal Year: 2003..nucleotide sequence of the gene encoding it, it has become clear that a class of protein molecules known as molecular chaperones can modulate the rate of proper protein folding events and determine the degree to which polypeptides enter ..
- An Oxygen-Sensing Network Involving Heme and ChaperonesLi Zhang; Fiscal Year: 2009..Thus, understanding how oxygen is sensed and how heme and molecular chaperones promote oxygen and global gene regulation is important for improving human health...
- Structure Function of the Mammalian Stress ProteinsWilliam Welch; Fiscal Year: 2004..Heat shock proteins, in their role as "molecular chaperones," participate in the synthesis, folding and intracellular transport of many, if not all, polypeptides...
