Genomes and Genes
Summary: 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.
Publications301 found, 100 shown here
- 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 ..
- 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...
- 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...
- Molecular chaperones in the cytosol: from nascent chain to folded proteinF Ulrich Hartl
Department of Cellular Biochemistry, Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D 82152 Martinsried, Germany
Science 295:1852-8. 2002Efficient folding of many newly synthesized proteins depends on assistance from molecular chaperones, which serve to prevent protein misfolding and aggregation in the crowded environment of the cell...
- Role of plant heat-shock proteins and molecular chaperones in the abiotic stress responseWangxia Wang
The Robert H Smith Institute of Plant Sciences and Genetics in Agriculture, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel
Trends Plant Sci 9:244-52. 2004
- 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...
- 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 ..
- 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 ..
- 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...
- ER stress and the unfolded protein responseMartin Schroder
School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK
Mutat Res 569:29-63. 2005..g. execution of differentiation and starvation programs...
- The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperonesX B Qiu
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China
Cell Mol Life Sci 63:2560-70. 2006..This review highlights the progress in studying the domains in DnaJ/Hsp40 proteins, introduces the mechanisms by which they interact with Hsp70s, and stresses their functional diversity...
- Molecular chaperones and protein quality controlBernd Bukau
Zentrum fur Molekulare Biologie, Universitat Heidelberg, 69120 Heidelberg, Germany
Cell 125:443-51. 2006..the removal of aggregates from the cytosol; reveal mechanisms for protein quality control in the endoplasmic reticulum; and provide new insight into two classes of molecular chaperones, the Hsp70 system and the AAA+ (Hsp100) unfoldases.
- ER stress and diseasesHiderou Yoshida
Department of Biophysics, Graduate School of Science, Kyoto University, Japan
FEBS J 274:630-58. 2007..In this review, I will summarize recent progress in this field. Molecules that regulate the ER stress response would be potential candidates for drug targets in various conformational diseases...
- 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...
- Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteinsJ R Glover
Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637, USA
Cell 94:73-82. 1998..coli. We conclude that Hsp104 has a protein remodeling activity that acts on trapped, aggregated proteins and requires specific interactions with conventional chaperones to promote refolding of the intermediates it produces...
- Protein quality control in the cytosol and the endoplasmic reticulum: brothers in armsAlexander Buchberger
Department of Biochemistry, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany
Mol Cell 40:238-52. 2010....
- HIV integration targeting: a pathway involving Transportin-3 and the nuclear pore protein RanBP2Karen E Ocwieja
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
PLoS Pathog 7:e1001313. 2011..Thus, our data support a model in which Gag-dependent engagement of the proper transport and nuclear pore machinery mediate trafficking of HIV complexes to sites of integration...
- 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...
- 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...
- 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...
- S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegenerationTakashi Uehara
Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
Nature 441:513-7. 2006..Thus, PDI prevents neurotoxicity associated with ER stress and protein misfolding, but NO blocks this protective effect in neurodegenerative disorders through the S-nitrosylation of PDI...
- 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....
- 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....
- 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...
- ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signalsJingshi Shen
Department of Biological Sciences, Columbia University, New York, NY 10027, USA
Dev Cell 3:99-111. 2002..reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecular chaperones. Upon ER stress, ATF6 translocates from the ER to the Golgi where it is processed to its active form...
- Ero1α regulates Ca(2+) fluxes at the endoplasmic reticulum-mitochondria interface (MAM)Tiziana Anelli
Universita Vita Salute San Raffaele, Milano, Italy
Antioxid Redox Signal 16:1077-87. 2012..How these multiple functions are integrated with one another in living cells remains unclear...
- Molecular chaperones and the stress of oncogenesisDick D Mosser
Department of Molecular Biology and Genetics, University of Guelph, Guelph, Ontario, Canada N1G 2W1
Oncogene 23:2907-18. 2004..The involvement of chaperones, therefore, in such diverse roles might suggest novel anticancer therapeutic approaches targeting heat-shock protein function for a broad spectrum of tumor types...
- 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...
- 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....
- Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosisXiaodong Wang
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Cell 127:803-15. 2006..The activity of cargo-associated chaperome components may be a common mechanism regulating folding for ER exit, providing a general framework for correction of misfolding disease...
- Protein targeting and degradation are coupled for elimination of mislocalized proteinsTara Hessa
Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 475:394-7. 2011..We propose that such coupling allows the fast tracking of MLPs for degradation without futile engagement of the cytosolic folding machinery...
- The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stressAmy S Lee
Department of Biochemistry and Molecular Biology and the USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 9176, USA
Methods 35:373-81. 2005..This can be achieved by measuring the Grp78 promoter activity or by measuring the level of Grp78 transcripts or GRP78 protein. These techniques can be applied to tissue culture cells as well as tissues and organs...
- 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...
- Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entryDaniël Splinter
Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands
PLoS Biol 8:e1000350. 2010....
- Structural and functional diversities between members of the human HSPB, HSPH, HSPA, and DNAJ chaperone familiesMichel J Vos
Department of Cell Biology, Section of Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Biochemistry 47:7001-11. 2008..The mechanism of action of the "classical", stress-inducible HSPs in serving as molecular chaperones preventing the irreversible aggregation of stress-unfolded or disease-related misfolded proteins is ..
- 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...
- Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperoneRongmin Zhao
Department of Biochemistry, Medical Sciences Building, 1 King s College Circle, University of Toronto, Toronto, ON, M5S 1A8, Canada
Cell 120:715-27. 2005..These cofactors interact physically and functionally with the conserved AAA(+)-type DNA helicases Rvb1/Rvb2, which are key components of several chromatin remodeling factors, thereby linking Hsp90 to epigenetic gene regulation...
- 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....
- Stress induction of GRP78/BiP and its role in cancerJianze Li
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, 90089 9176, USA
Curr Mol Med 6:45-54. 2006..This review summarizes the transcriptional regulation of Grp78, the molecular basis for the cytoprotective function of GRP78 and its role in cancer progression, drug resistance and potential future cancer therapy...
- 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...
- HSP90 and its R2TP/Prefoldin-like cochaperone are involved in the cytoplasmic assembly of RNA polymerase IISéverine Boulon
Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee, UK
Mol Cell 39:912-24. 2010..hSpagh also bound the free RPA194 subunit of RNA polymerase I, suggesting a general role in assembling RNA polymerases...
- 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....
- The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradationG C Meacham
Department of Cell Biology and Cystic Fibrosis Center, University of Alabama Medical Center, 1918 University Boulevard, Birmingham, Alabama 35294 0005, USA
Nat Cell Biol 3:100-5. 2001..CHIP is a co-chaperone that converts Hsc70 from a protein-folding machine into a degradation factor that functions in endoplasmic-reticulum quality control...
- 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...
- 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...
- Protein folding and modification in the mammalian endoplasmic reticulumIneke Braakman
Cellular Protein Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands
Annu Rev Biochem 80:71-99. 2011..How these various machineries interact during the normal pathway of folding and protein secretion is the subject of this review...
- Dissecting the role of the mitochondrial chaperone mortalin in Parkinson's disease: functional impact of disease-related variants on mitochondrial homeostasisLena F Burbulla
DZNE, German Center for Neurodegenerative Diseases, Tubingen, Germany
Hum Mol Genet 19:4437-52. 2010..Our results support the role of this mitochondrial chaperone in neurodegeneration and underscore the concept of impaired mitochondrial protein quality control in PD...
- A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2R Mahajan
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Cell 88:97-107. 1997..Inhibition of nuclear protein import resulting from antibodies directed at NPC-associated RanGAP1 cannot be overcome by soluble cytosolic RanGAP1, indicating that GTP hydrolysis by Ran at RanBP2 is required for nuclear protein import...
- Protein disaggregation mediated by heat-shock protein Hsp104D A Parsell
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637
Nature 372:475-8. 1994..Rather, Hsp104 functions in a manner not previously described for other heat-shock proteins: it mediates the resolubilization of heat-inactivated luciferase from insoluble aggregates...
- A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activityPhilippe Cloutier
Institut de recherches cliniques de Montreal IRCM, Montreal, Quebec, Canada
PLoS Genet 9:e1003210. 2013..Overall, this report uncovers a new role for protein methylation as a regulatory pathway for molecular chaperones and defines a novel regulatory mechanism for the chaperone VCP, whose deregulation is causative of ..
- Chaperone networks in protein disaggregation and prion propagationJuliane Winkler
Center for Molecular Biology of the University of Heidelberg and German Cancer Research Center, DKFZ ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg D 69120, Germany
J Struct Biol 179:152-60. 2012....
- Cellular strategies of protein quality controlBryan Chen
Department of Biology and BioX Program, Stanford University, Stanford, California 94305, USA
Cold Spring Harb Perspect Biol 3:a004374. 2011..An elaborate network of molecular chaperones and protein degradation factors continually monitor and maintain the integrity of the proteome...
- 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...
- In vivo monitoring of the prion replication cycle reveals a critical role for Sis1 in delivering substrates to Hsp104Kimberly A Tipton
California Institute of Quantitative Biomedical Science, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94158 2542, USA
Mol Cell 32:584-91. 2008..Our data suggest that yeast prion replication is a natural extension of chaperone activity in dissolving amorphous aggregates, distinguished from its ancestral reaction by the ordered, self-propagating structure of the substrate...
- 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...
- Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activationRamachandra K Reddy
Department of Biochemistry and Molecular Biology and the USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90089 9176, USA
J Biol Chem 278:20915-24. 2003..Lastly, a GRP78 mutant deleted of its ATP binding domain fails to bind procaspase-7 and loses its protective effect against etoposide-induced apoptosis...
- 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....
- 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...
- 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...
- DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formationShoshana Shendelman
Department of Pathology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, College of Physicians and Surgeons, New York, New York, USA
PLoS Biol 2:e362. 2004..We further demonstrate that DJ-1 chaperone activity in vivo extends to alpha-synuclein, a protein implicated in PD pathogenesis...
- The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cellsJ Li
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA
Cell Death Differ 15:1460-71. 2008..Thus, these studies uncover 3-MA as an inhibitor of UPR activation and establish GRP78 as a novel obligatory component of autophagy in mammalian cells...
- Enzymatic blockade of the ubiquitin-proteasome pathwayRobert Ernst
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
PLoS Biol 8:e1000605. 2011..Our data underscore the necessity of a DUB activity for completion of the dislocation reaction and provide a new means of inhibition of proteasomal proteolysis with reduced cytotoxicity...
- Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56Robert Driscoll
Wellcome Trust and Cancer Research U K Gurdon Institute and the Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
Science 315:649-52. 2007..These data establish Rtt109p as a member of a new class of histone acetyltransferases and show that its actions are critical for cell survival in the presence of DNA damage during S phase...
- 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...
- Perturbation of host nuclear membrane component RanBP2 impairs the nuclear import of human immunodeficiency virus -1 preintegration complex (DNA)Ruonan Zhang
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America
PLoS ONE 5:e15620. 2010..RanBP2 could be a potential target for efficient inhibition of HIV...
- Evolution of the chaperone/usher assembly pathway: fimbrial classification goes GreekSean Paul Nuccio
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave, Davis, CA 95616 8645, USA
Microbiol Mol Biol Rev 71:551-75. 2007..The proposed classification system offers a simple and convenient method for assigning newly discovered chaperone/usher systems to one of the six major phylogenetic groups...
- Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complexDavid Reverter
Structural Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
Nature 435:687-92. 2005....
- An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cellYunchen Gong
Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
Mol Syst Biol 5:275. 2009b>Molecular chaperones are known to be involved in many cellular functions, however, a detailed and comprehensive overview of the interactions between chaperones and their cofactors and substrates is still absent...
- Protein folding in the cytoplasm and the heat shock responseR Martin Vabulas
Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D 82152 Martinsried, Germany
Cold Spring Harb Perspect Biol 2:a004390. 2010..In the cell, this fundamental process is aided by molecular chaperones, which act in preventing protein misfolding and aggregation...
- Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complexMaruf M U Ali
Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
Nature 440:1013-7. 2006..Contrary to expectations, the closed Hsp90 would not enclose its client proteins but provides a bipartite binding surface whose formation and disruption are coupled to the chaperone ATPase cycle...
- β-Barrel membrane protein assembly by the Bam complexChristine L Hagan
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Annu Rev Biochem 80:189-210. 2011....
- Molecular chaperones and stress-inducible protein-sorting factors coordinate the spatiotemporal distribution of protein aggregatesLiliana Malinovska
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
Mol Biol Cell 23:3041-56. 2012..the subcellular distribution of misfolded proteins as a function of the cytosolic concentrations of molecular chaperones and protein-sorting factors...
- SIRT1 protects against α-synuclein aggregation by activating molecular chaperonesGizem Donmez
Paul F Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Neurosci 32:124-32. 2012..Thus, SIRT1 responds to α-synuclein aggregation-induced stress by activating molecular chaperones to protect against disease.
- Altered Hsp90 function in cancer: a unique therapeutic opportunityRochelle Bagatell
Department of Pediatrics and Hematology Oncology, Arizona Health Sciences Center, Room 5341, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
Mol Cancer Ther 3:1021-30. 2004b>Molecular chaperones or so-called heat shock proteins serve as central integrators of protein homeostasis within cells...
- Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentationJuliane Winkler
Center for Molecular Biology of the University of Heidelberg and German Cancer Research Center, DKFZ ZMBH Alliance, Universitat Heidelberg, Heidelberg D 69120, Germany
J Cell Biol 198:387-404. 2012..Our findings indicate a conserved mechanism of Hsp70-Hsp100 cooperation at the surface of protein aggregates and prion fibrils...
- Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alphaClaudio Hetz
Howard Hughes Medical Institute, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA
Science 312:572-6. 2006..Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR...
- 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...
- 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...
- 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...
- Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutaseT D Rae
Department of Chemistry and Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA
Science 284:805-8. 1999..These results indicate that intracellular [Cu]free is limited to less than one free copper ion per cell and suggest that a pool of free copper ions is not used in physiological activation of metalloenzymes...
- 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....
- 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...
- 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 ..
- Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperonesTakunari Yoneda
Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
J Cell Sci 117:4055-66. 2004..These observations support the existence of a mitochondrial unfolded protein response that couples mitochondrial chaperone gene expression to changes in the protein handling environment in the organelle...
- HTRA proteases: regulated proteolysis in protein quality controlTim Clausen
Research Institute of Molecular Pathology, Dr Bohrgasse 7, A 1030 Vienna, Austria
Nat Rev Mol Cell Biol 12:152-62. 2011....
- H-NS: a modulator of environmentally regulated gene expressionT Atlung
Department of Chemistry and Life Sciences, Roskilde University, Denmark
Mol Microbiol 24:7-17. 1997..Finally, we summarize the evolutionary and functional relationship between H-NS and the homologous StpA...
- 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...
- Ran-dependent docking of importin-beta to RanBP2/Nup358 filaments is essential for protein import and cell viabilityMasakazu Hamada
Department of Biochemistry and Molecular Biology and 2 Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA
J Cell Biol 194:597-612. 2011..These data suggest that a critical function of RanBP2 is to capture recycling RanGTP-importin-β complexes at cytoplasmic fibrils to allow for adequate cNLS-mediated cargo import...
- Structural analysis of a monomeric form of the twin-arginine leader peptide binding chaperone Escherichia coli DmsDCharles M Stevens
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada
J Mol Biol 389:124-33. 2009..coli DmsA and the most conserved regions on the surface of EcDmsD...
- Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteinsHassane S McHaourab
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232 0615, USA
Biochemistry 48:3828-37. 2009Small heat shock proteins (sHSP) make up a remarkably diverse group of molecular chaperones possessing a degree of structural plasticity unparalleled in other protein superfamilies...
- An interdomain sector mediating allostery in Hsp70 molecular chaperonesRobert G Smock
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA
Mol Syst Biol 6:414. 2010Allosteric coupling between protein domains is fundamental to many cellular processes. For example, Hsp70 molecular chaperones use ATP binding by their actin-like N-terminal ATPase domain to control substrate interactions in their C-..
- 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..These data identify BAT3 as a cellular ligand for NKp30. 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...
- 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...
- 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...
- 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...
- 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...
- HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53Toru Sasaki
The Campbell Family Institute for Breast Cancer Research CFIBCR, Ontario Cancer Institute OCI, University Health Network, Toronto, Ontario M5G 2C1, Canada
Genes Dev 21:848-61. 2007..Our data indicate that Bat3 is a novel and essential regulator of p53-mediated responses to genotoxic stress, and that Bat3 controls DNA damage-induced acetylation of p53...
- Chemical and biological approaches synergize to ameliorate protein-folding diseasesTing Wei Mu
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Cell 134:769-81. 2008..It may be possible to ameliorate loss-of-function diseases by using proteostasis regulators alone or in combination with a pharmacologic chaperone...
- Dietary Cholesterol and Defects in Cholesterol SynthesisROBERT DAVID STEINER; Fiscal Year: 2013..We further hypothesize that statins, bile acids, antioxidants and molecular chaperones selectively restore SLOS cell metabolism and function...
- Role of Heat Shock Transcription Factor Hsf1 in TumorigenesisNahid F Mivechi; Fiscal Year: 2013..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 ..
- Effect of HIV protease inhibitor on alcohol induced ER stress and liver injury.Cheng Ji; Fiscal Year: 2013..stress response in these cell types;(5) to determine in vitro and in vivo the effectiveness of protective molecular chaperones (e.g. 4-phenylbutyrate ) in HIV PI- induced ER stress and liver injury...
- Characterization of the ER associated Biogenesis and Degradation of ENaCTeresa M Buck; Fiscal Year: 2013..My previous work has shown that the degradation of ENaC requires a unique complement of molecular chaperones. For example, the ER lumenal Hsp40s are required for ENaC degradation, but the Hsp70, BiP for which Hsp40s ..
- Novel Chaperone Mechanism for Platelet DisorderZihai Li; Fiscal Year: 2010..However, little is known on how GPIb-IX-V macromolecular complex is assembled and what are the roles of molecular chaperones in this process...
- Mechanisms of assembly of photoreceptor G protein complexesBarry M Willardson; Fiscal Year: 2013..An understanding of the way these protein complexes are brought together is necessary to develop treatments that would allow the complexes to assemble and function despite the mutations. ..
- The differential regulation of poly(ADP-ribose) in cancer and its role in proteinKRISTIN ANNE KRUKENBERG; Fiscal Year: 2013..This study will also determine the potential of pADPr levels in predicting drug sensitivity and identify possible new strategies for the use of PARP inhibitors in the clinic. ..
- Heat shock protein 90 antagonist-based therapy of mantle cell lymphomaKapil Bhalla; Fiscal Year: 2012..This strategy involves combinations of treatments with heat shock protein 90 and proteosome inhibitors designed to target protein folding and degradation in MCL cells. ..
- DEVELOPMENT AND MAINTENANCE OF LENS TRANSPARENCYJOHN IRWIN CLARK; Fiscal Year: 2013..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. ..
- Identification of key tumor cell-released factors that induce cachexiaYi Ping Li; Fiscal Year: 2013..Traditionally, HSPs are primarily known as intracellular molecular chaperones for protein folding, assembly, and translocation, thus making them cytoprotective...
- Defining the role of proteostasis pathways in cancer drug resistanceERICA LYNN CAIN; Fiscal Year: 2013..is missing large parts of the wild-type protein and likely has increased instability and dependence on molecular chaperones. Additionally, the expression of mutated versions of BRCA2 from multiple alleles in PARPi-resistant cells ..
- Unfolded Protein Response as a Therapeutic Target for ADRP Animal ModelsMarina Gorbatyuk; Fiscal Year: 2013..This approach may overcome the genetic diversity of this disease and reveal the pathways of cell death that lead from mutation to retinal degeneration. ..
- Mitochondrial chaperones mortalin and Tid1 in protein degradation Carolyn K Suzuki; Fiscal Year: 2012..control is composed of ATP-dependent proteases, which degrade misfolded and damaged proteins, as well as molecular chaperones, which mediate protein folding and facilitate protein degradation...
- Dynamics of Transcriptional RegulationElena Zelin; Fiscal Year: 2011..Hence, investigation of molecular mechanisms of transcriptional control will potentially facilitate design of drug-and gene-based therapeutic strategies to treat these abnormalities. ..
- Diabetic retinopathy: sigma receptor 1 (??R1) as a novel therapeutic target.Sylvia B Smith; Fiscal Year: 2013..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. ..
- Novel Hsp90 Inhibitors to Reduce Misfolded Proteins in Alzheimer's DiseaseMary L Michaelis; Fiscal Year: 2011..Consequently much recent research has been focused on molecular chaperones, the cellular machinery responsible for maintaining protein folding or mediating the degradation of ..
- Fundamental mechanisms of protein kinase activation loop autophosphorlyationVaughn Cleghon; Fiscal Year: 2013..This knowledge will increase our understanding of these processes and will allow us to design small molecule activators and inhibitors of the DYRKs that are likely to be of therapeutic use. ..
- Lung Endothelial Cell Apoptosis and EmphysemaSHARON IRENE SMITH ROUNDS; Fiscal Year: 2013..demonstrated that EC apoptosis occurs despite activation of the unfolded protein response (UPR) when ER molecular chaperones are decreased...
- Cyclophilin B as a therapeutic target in glioblastomaRichard J Bram; Fiscal Year: 2013..Together, these studies will test the feasibility of CypB as a novel target for therapy of GBM, and set the stage for transition to clinical studies in humans. ..
- Quantitative analysis of the evolving genotype-to-phenotype mapDANIEL JAROSZ; Fiscal Year: 2012..They will also expose an Achilles'heel common to all cancers - addiction to factors that enable maintenance of massive mutation loads. ..
- Quantitative analysis of the evolving genotype-to-phenotype mapDANIEL JAROSZ; Fiscal Year: 2013..They will also expose an Achilles'heel common to all cancers - addiction to factors that enable maintenance of massive mutation loads. ..
- Regulation of TLR4 Signaling in Enterocytes in Necrotizing EnterocolitisAmin Afrazi; Fiscal Year: 2013..The current proposal seeks to test whether increasing levels of Heat Shock Protein 70 can serve as a novel therapeutic approach for infants with this devastating disorder. ..
- MOLECULAR PATHOLOGY OF VASCULAR INJURYDario C Altieri; Fiscal Year: 2013..We found that molecular chaperones of the Heat Shock Protein-90 (Hsp90) family accumulate in mitochondria, associate with component(s) of the ..
- Mechanisms of Sensory Hair Cell Death and SurvivalLisa L Cunningham; Fiscal Year: 2010..Understanding these mechanisms will guide the development of therapies aimed at preventing hearing loss caused by ototoxic drugs. ..
- MOLECULAR STUDIES OF RETINAL DEGENERATION IN DROSOPHILANansi J Colley; Fiscal Year: 2013..The endoplasmic reticulum (ER) contains a wide variety of molecular chaperones, folding sensors and enzymes, as well as escort proteins that facilitate the early stages of protein ..
- Role of heat shock protein 90 in alcoholic liver diseasePranoti Mandrekar; Fiscal Year: 2013..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 ..
- Novel Molecular Therapies of Prostate CancerDario C Altieri; Fiscal Year: 2013..connects three fundamental pathways of cellular homeostasis: mitochondrial control of cell survival by molecular chaperones, pleiotropic signaling by integrin adhesion receptors, and local regulation of gene expression in bone ..
- Relative Roles of HSP70 and HSP25 in the Modulation of Renal InjuryRajasree Sreedharan; Fiscal Year: 2010..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 ..
- Homocysteine, ER Stress and Alcoholic Liver Injury.Neil Kaplowitz; Fiscal Year: 2013..Determine the effectiveness of molecular chaperones in inhibiting alcohol and homocysteine-induced ER stress and steatohepatitis: this work includes in vitro ..
- Aging Research at the 2010 through 2014 ASHEcon Biennial ConferencesJody L Sindelar; Fiscal Year: 2013ABSTRACT This proposal is a request for partial financial support for a meeting on Molecular Chaperones and Stress Responses to be held from May 4 - 8, 2010 at Cold Spring Harbor Laboratory...
- MOLECULAR CHAPERONES AND PROTEIN DEGRADATIONAlfred L Goldberg; Fiscal Year: 2013..We now hope to solve its structure and define the detailed mechanisms of these two types of AAA ATPases and of the promising new antibiotic, Novo23, that we found uncouples ATP hydrolysis by ClpC1 from proteolysis by ClpP1P2. ! ..
- Regulation and function of mammalian HSF4 in vivoNahid F Mivechi; Fiscal Year: 2012..A hallmark in the pathogenesis of cancer is increased expression of heat shock proteins (Hsps) and other molecular chaperones;this is considered to be an adaptive response to enhanced tumor cell survival...
- 2010 Cold Spring Harbor Laboratory Conference on Molecular Chaperones and StressDavid J Stewart; Fiscal Year: 2012ABSTRACT This proposal is a request for partial financial support for a meeting on Molecular Chaperones and Stress Responses to be held from May 4 - 8, 2010 at Cold Spring Harbor Laboratory...
- Rational Design and Clinical Development of Shepherdin: A Novel Anti-Cancer AgentDario C Altieri; Fiscal Year: 2013..abstract_text> ..
- Structural Biology of U-box E3 Ubiquitin LigasesWalter J Chazin; Fiscal Year: 2013..This information has the potential to open up new therapeutic avenues for treatment of neurodegenerative diseases and certain cancers based on regulating the cellular level of these key molecular chaperones.
- Genetic Basis of Non-Familial IgA NephropathyTongzhong Ju; Fiscal Year: 2012....
- The Cyto-Protective Role of Hexokinase II During Metabolic StressJONATHAN MICHAEL GALL; Fiscal Year: 2012..The proposed studies will provide molecular insights into the mechanism of renal cell death and may promote the development of therapeutic interventions for treating acute, ischemic renal failure. ..
- Mechanism of Myosin Chaperone UNC-45: Structural, Functional &Genetic ApproachesSanford I Bernstein; Fiscal Year: 2013..Overall, our integrative analysis will provide important insights into the mechanism of action of UNC-45 and its role in muscle development, stasis and stress. ..
- Chaperone therapeutics for the treatment of DPNRick T Dobrowsky; Fiscal Year: 2013..The outcome of this work will further develop and identify small molecule C-terminal Hsp90 inhibitors that decrease neurodegeneration in the absence of significant neurotoxicity. ..
- Chaperones in Diabetic Peripheral NeuropathyRick T Dobrowsky; Fiscal Year: 2013..The outcomes of our work will provide fundamental molecular insight into how Hsp70 paralogs improve sensory neuron bio- energetics and validate that modulating molecular chaperones is a viable approach to medically manage DPN.
- Assembly and Trafficking of Heterotrimeric G Proteins in Vertebrate PhotoreceptorMaxim Sokolov; Fiscal Year: 2013DESCRIPTION (provided by applicant): Our long-term research objective is to understand the roles of molecular chaperones in vertebrate photoreceptors...
- Role of oligomeric alpha-synuclein in synucleinopathiesPamela J McLean; Fiscal Year: 2013..in disease pathogenesis with a view to determining the effect of disease- related modifications and molecular chaperones on 1syn oligomer formation and subcellular location (aim 1 &2)...
- Alpha-Crystallin and CataractogensisJoseph Horwitz; Fiscal Year: 2009..These are excellent models for understanding the biochemical and biophysical changes that occur in age-related human cataract. ..
- Posttranslational processing of tau: function & dysfunc.Gail Johnson; Fiscal Year: 2009..of specific sites on tau affect tau-microtubule interactions, tau oligomerization, tau interaction with molecular chaperones (and thus its functional state), and tau turnover through the ubiquitin-proteasome system...
- Streamlined Structures of Human Integral Membrane Proteins at Atomic ResolutionStephen G Aller; Fiscal Year: 2011..We have engineered molecular chaperones to enable the production of the most difficult human IMPs in folded mature form using a low-cost yeast ..
- Mechanistic basis and potential therapies for myosin storage myopathySanford I Bernstein; Fiscal Year: 2013..3) Attempt to ameliorate disease phenotypes in organisms a) by over-expressing the molecular chaperones alphaB-crystallin, Hsp70, Hsp90 or UNC-45 (all known to aid in myosin folding and/or protection from stress)..
- Maintenance of Mitochondrial Protein Folding as an Aging EffectorCOLE MICHAEL HAYNES; Fiscal Year: 2013..during organelle remodeling and stress, the mitochondrial protein-folding environment must be maintained by molecular chaperones and proteases...
- Sensor Mechanisms of HSF ActivationEvgeny Nudler; Fiscal Year: 2013..The hallmark of the HS response is the rapid and robust induction of HS genes, many of which encoding molecular chaperones. Heat shock proteins (HSPs) have been also implicated in a variety of pathological situations including ..
- Mechanisms of VCP/p97 and Proteasomal pathway in COPD pathogenesisNeeraj Vij; Fiscal Year: 2010..We anticipate improving our understanding of COPD lung disease and contributing to the development of new and better treatments. (End of Abstract) ..
- Cytoprotective mechanism against misfolded SOD1-induced toxicityCHERYL HO YUNG; Fiscal Year: 2013..neurodegenerative diseases and are normally handled by efficient protein quality control systems including molecular chaperones and the ubiquitin-proteasome system...
- Elucidating the Relations of Heat Shock Factors, Molecular Chaperones and PrionsLiming Li; Fiscal Year: 2012..are evolutionally conserved transcriptional factors responsible for the biosynthesis of the majority of molecular chaperones, which are essential for protecting cells from extreme harsh conditions by refolding or dis-aggregating ..
- Tonicity signaling to TonEBP transcription factorH Moo Kwon; Fiscal Year: 2012..This information will provide new opportunity to develop therapy for renal diseases such as diabetic nephropathy and acute renal failure. ..
- CHIP: A link between the chaperone and proteasome systemJonathan C Schisler; Fiscal Year: 2013..provided by applicant): 70- and 90-kDa heat shock proteins (Hsps) are best known by their roles as molecular chaperones, participating in the folding, maturation, and proper subcellular targeting of nascent proteins or, ..
- THE TUMOR ANTIGENS TN AND SIALYLTN IN HUMAN COLORECTAL CARCINOMATongzhong Ju; Fiscal Year: 2013..This project will define the molecular basis for Tn and STn expression in CRC and their potential as novel glycan biomarkers for human colon cancer. ..
- Evolving membrane proteins for high-level expression in modified mammalian cellsMichael J Betenbaugh; Fiscal Year: 2013..In parallel, mammalian production hosts will be engineered with anti-apoptotic proteins, molecular chaperones, and transcription factors capable of improving protein processing...
- Cellular Processing of Optineurin, the Product of a Glaucoma GeneBeatrice Y J T Yue; Fiscal Year: 2012..b>Molecular chaperones associated with endogenous optineurin will be identified...
- Novel Targeted Therapy for AMLKapil Bhalla; Fiscal Year: 2013..Overall, these aims will establish NPM1 as a 'druggable'target and pave the way for performing high throughput screening and development of novel compounds that target NPM1 for the therapy of AML expressing mtNPM1. ..
- Role of co-chaperone, BAG3, in muscle degeneration under physiological stressShinichi Takayama; Fiscal Year: 2010Project Summary. BAG3 is a member of co-chaperones that binds to and regulates Hsp70-family molecular chaperones. BAG3 is expressed in muscle and has been reported to possess anti-apoptotic...
- A Systems Approach to Stress Biology and Proteostasis NetworksRichard I Morimoto; Fiscal Year: 2013..2) At the cellular level, to characterize the tissue-specific expression of the family of genes encoding molecular chaperones to elucidate the underlying strategy for chaperone networks in response to stress, during development, and ..
- Selective and dual-acting Hsp90 and TRAP1 inhibitorsDuncan McRee; Fiscal Year: 2010....
- Hsp90 Regulates EphA2 Signaling and Cell Migration in GlioblastomaJennifer S Isaacs; Fiscal Year: 2012..Our studies will potentially lead to rational molecular-targeted therapeutic approaches to improve GBM survival. ..
- The mechanism of action of a NudC domain small heat shock proteinNicholas J Kaplinsky; Fiscal Year: 2010..Protein misfolding is a characteristic feature of many human diseases, so understanding how BOBBER1 functions will provide valuable insights into this important biological process. ..
- ANNUAL BIOMEDICAL RESEARCH WORKSHOPSJOSE TORRES RUIZ; Fiscal Year: 1999..He is also MBRS Program Director (since 1993). He has an active research program with an interest in molecular chaperones expression in activated human T cells. He lists 6 papers published or in press since 1992...
- Celestrols for Treatment of Neurodegenerative DiseasesRichard Silverman; Fiscal Year: 2007DESCRIPTION (provided by applicant): The 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&..
- High Resolution Analysis of Ribosome-Bound Nascent Polypeptides by NMRSilvia Cavagnero; Fiscal Year: 2009..competition between the tendency to experience intramolecular hydrophobic collapse and the tendency to bind molecular chaperones during translation, the following specific aims will be pursued: (1) NMR structural characterization of ..
- Heat Shock Protein Function for Drug DiscoveryLuke Whitesell; Fiscal Year: 2003..These ubiquitously expressed molecular chaperones are not mutated in cancer...
- 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...