hsc70 heat shock proteins


Summary: A constitutively expressed subfamily of the HSP70 heat-shock proteins. They preferentially bind and release hydrophobic peptides by an ATP-dependent process and are involved in post-translational PROTEIN TRANSLOCATION.

Top Publications

  1. Watanabe K, Tachibana M, Kim S, Watarai M. Participation of ezrin in bacterial uptake by trophoblast giant cells. Reprod Biol Endocrinol. 2009;7:95 pubmed publisher
    ..However, the mechanism of bacterial uptake by TG cells is not completely understood. Here we identified ezrin, a member of ezrin-radixin-moesin (ERM) protein family, as a molecule associated with Hsc70...
  2. Guerrero C, Bouyssounade D, Zárate S, Isa P, López T, Espinosa R, et al. Heat shock cognate protein 70 is involved in rotavirus cell entry. J Virol. 2002;76:4096-102 pubmed
    ..We propose that the functional rotavirus receptor is a complex of several cell surface molecules that include, among others, hsc70. ..
  3. Chen S, Bawa D, Besshoh S, Gurd J, Brown I. Association of heat shock proteins and neuronal membrane components with lipid rafts from the rat brain. J Neurosci Res. 2005;81:522-9 pubmed
  4. Popoff V, Mardones G, Bai S, Chambon V, Tenza D, Burgos P, et al. Analysis of articulation between clathrin and retromer in retrograde sorting on early endosomes. Traffic. 2009;10:1868-80 pubmed publisher
    ..Our combined data suggest a model according to which the functions in retrograde sorting on early endosomes of SNX1/retromer and clathrin are articulated by RME-8, and possibly also by Hrs. ..
  5. Watanabe K, Tachibana M, Kim S, Watarai M. EEVD motif of heat shock cognate protein 70 contributes to bacterial uptake by trophoblast giant cells. J Biomed Sci. 2009;16:113 pubmed publisher
    ..These molecules may be useful in the development of methods for preventing infectious abortion. ..
  6. Page N, Schall N, Strub J, Quinternet M, Chaloin O, Decossas M, et al. The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by gammadelta T cells. PLoS ONE. 2009;4:e5273 pubmed publisher
    ..Expression of inflammation-linked genes is rapidly regulated in CD4(+) T cells. This work led us to identify a powerful pathway taken by a newly-designed therapeutic peptide to immunomodulate lupus autoimmunity. ..
  7. Cazalé A, Clement M, Chiarenza S, Roncato M, Pochon N, Creff A, et al. Altered expression of cytosolic/nuclear HSC70-1 molecular chaperone affects development and abiotic stress tolerance in Arabidopsis thaliana. J Exp Bot. 2009;60:2653-64 pubmed publisher
  8. Ao L, Zou N, Cleveland J, Fullerton D, Meng X. Myocardial TLR4 is a determinant of neutrophil infiltration after global myocardial ischemia: mediating KC and MCP-1 expression induced by extracellular HSC70. Am J Physiol Heart Circ Physiol. 2009;297:H21-8 pubmed publisher
    ..TLR4 mediates myocardial chemokine expression, and the mechanisms involve extracellular HSC70. These results imply the HSC70-TLR4 interaction as a novel mechanism underlying the myocardial chemokine response to global I/R. ..
  9. Asano Y, Akiyama K, Tsuji T, Takahashi S, Noguchi J, Kunieda T. Characterization and linkage mapping of an ENU-induced mutant mouse with defective spermatogenesis. Exp Anim. 2009;58:525-32 pubmed
    ..Therefore, the gene responsible for the repro23 mutation is suggested to be a novel gene which plays an essential role in mammalian spermatogenesis. ..

More Information


  1. Massey A, Williamson D, Browne H, Murray J, Dokurno P, Shaw T, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 2010;66:535-45 pubmed publisher
    ..The factors determining whether or not cells apoptose in response to Hsp90 inhibition or the combination of Hsp90 plus Hsc70/Hsp70 inhibition remain to be determined. ..
  2. Sharp A, Crabb S, Johnson P, Hague A, Cutress R, Townsend P, et al. Thioflavin S (NSC71948) interferes with Bcl-2-associated athanogene (BAG-1)-mediated protein-protein interactions. J Pharmacol Exp Ther. 2009;331:680-9 pubmed publisher
    ..Inhibition of BAG-1 function may be an attractive strategy to inhibit the growth of BAG-1-overexpressing cancers, and further screens of additional compound collections may be warranted. ..
  3. Lederman M, Weiss A, Chowers I. Association of neovascular age-related macular degeneration with specific gene expression patterns in peripheral white blood cells. Invest Ophthalmol Vis Sci. 2010;51:53-8 pubmed publisher
    ..Such altered expression may potentially serve as a biomarker for the disease. These data support the involvement of systemic immune response in the pathogenesis of AMD. ..
  4. Brkljacic J, Zhao Q, Meier I. WPP-domain proteins mimic the activity of the HSC70-1 chaperone in preventing mistargeting of RanGAP1-anchoring protein WIT1. Plant Physiol. 2009;151:142-54 pubmed publisher
    ..Taken together, our data suggest that both HSC70-1 and the WPP-domain proteins play a role in facilitating WIT1 nuclear envelope targeting, which is, to our knowledge, the first described in planta activity for the WPP-domain proteins. ..
  5. Takino J, Kobayashi Y, Takeuchi M. The formation of intracellular glyceraldehyde-derived advanced glycation end-products and cytotoxicity. J Gastroenterol. 2010;45:646-55 pubmed publisher
    ..Furthermore, intracellular Glycer-AGEs increased the CRP mRNA concentration. These results suggest that intracellular Glycer-AGEs play important roles in promoting inflammation and hepatocellular death. ..
  6. Alam M, Andrina B, Tay T, Tsunekawa N, Kanai Y, Kurohmaru M. Single administration of di(n-butyl) phthalate delays spermatogenesis in prepubertal rats. Tissue Cell. 2010;42:129-35 pubmed publisher
    ..These results lead us to the postulation that a single administration of DBP to prepubertal rats delays maturation of spermatogenic cells, even after completion of first wave of spermatogenesis. ..
  7. Jinwal U, O Leary J, Borysov S, Jones J, Li Q, Koren J, et al. Hsc70 rapidly engages tau after microtubule destabilization. J Biol Chem. 2010;285:16798-805 pubmed publisher
    ..Thus, under normal circumstances, MC1 formation may be a protective conformation facilitated by Hsc70. However, in a diseased environment, Hsc70 may preserve Tau in a more unstructured state, perhaps facilitating its pathogenicity. ..
  8. Hinitt C, Wood J, Lee S, Williams A, Howarth J, Glover C, et al. BAG-1 enhances cell-cell adhesion, reduces proliferation and induces chaperone-independent suppression of hepatocyte growth factor-induced epidermal keratinocyte migration. Exp Cell Res. 2010;316:2042-60 pubmed publisher
    ..These findings are the first to suggest that BAG-1 plays a role in regulating cell-cell adhesion and suggest an important function in epidermal cohesion. ..
  9. Yan F, Xia D, Hu J, Yuan H, Zou T, Zhou Q, et al. Heat shock cognate protein 70 gene is required for prevention of apoptosis induced by WSSV infection. Arch Virol. 2010;155:1077-83 pubmed publisher
  10. Park H, Mylvaganum M, McPherson A, Fewell S, Brodsky J, Lingwood C. A soluble sulfogalactosyl ceramide mimic promotes Delta F508 CFTR escape from endoplasmic reticulum associated degradation. Chem Biol. 2009;16:461-70 pubmed publisher
    ..AdaSGC also increased cellular endogenous SGC levels. SGC in the lung, liver, and kidney was severely depleted in Delta F508CFTR compared with wtCFTR mice, suggesting a role for CFTR in SGC biosynthesis. ..
  11. Ogata T, Oishi Y, Higashida K, Higuchi M, Muraoka I. Prolonged exercise training induces long-term enhancement of HSP70 expression in rat plantaris muscle. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1557-63 pubmed publisher
    ..These findings demonstrate that prolonged training can induce long-term enhancement of HSP70 expression without change at the mRNA level in skeletal muscle. ..
  12. Unterluggauer H, Micutkova L, Lindner H, Sarg B, Hernebring M, Nystrom T, et al. Identification of Hsc70 as target for AGE modification in senescent human fibroblasts. Biogerontology. 2009;10:299-309 pubmed publisher
    ..Using 2D-Gel electrophoresis and Western Blot we found that heat shock cognate protein 70 is a bona fide target for AGE modification in human fibroblasts. ..
  13. Chen Y, Chen Y, Chow L, Tsai Y, Chen P, Huang C, et al. Heat shock protein 72 is associated with the hepatitis C virus replicase complex and enhances viral RNA replication. J Biol Chem. 2010;285:28183-90 pubmed publisher
    ..The fact that the host chaperone protein Hsp72 is involved in HCV RNA replication may represent a therapeutic target for controlling virus production. ..
  14. Hishiya A, Kitazawa T, Takayama S. BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress. Circ Res. 2010;107:1220-31 pubmed publisher
    ..These proteins are possible targets for further research to identify therapies for myofibrillar myopathy or other degenerative diseases. ..
  15. Mak S, McCormack A, Manning Bog A, Cuervo A, Di Monte D. Lysosomal degradation of alpha-synuclein in vivo. J Biol Chem. 2010;285:13621-9 pubmed publisher
    ..It is conceivable that these neuronal mechanisms of protein clearance play an important role in neurodegenerative processes characterized by abnormal alpha-synuclein buildup. ..
  16. Lu T, Huang G, Wang H, Chen J, Hsu H, Lu T. Hispolon promotes MDM2 downregulation through chaperone-mediated autophagy. Biochem Biophys Res Commun. 2010;398:26-31 pubmed publisher
    ..Meanwhile, inhibition of Hsc70 using siRNA attenuated hispolon-induced MDM2 downregulation. Our study provides the first example of the ability of hispolon to mediate MDM2 downregulation in lysosomes through the CMA pathway. ..
  17. Zumaquero E, Munoz P, Cobo M, Lucena G, Pavón E, Martin A, et al. Exosomes from human lymphoblastoid B cells express enzymatically active CD38 that is associated with signaling complexes containing CD81, Hsc-70 and Lyn. Exp Cell Res. 2010;316:2692-706 pubmed publisher
    ..In conclusion, the present study indicates that CD38 localizes to MR, where it promotes cell signaling, and it is exported out of the cells through the exosome-mediated exocytic pathway, where it may act as an intercellular messenger. ..
  18. Lai I, Lin T, Yao Y, Lin C, Hsieh M, Yang W. Histone deacetylase 10 relieves repression on the melanogenic program by maintaining the deacetylation status of repressors. J Biol Chem. 2010;285:7187-96 pubmed publisher
    ..Our results not only show that HDAC10 regulates melanogenesis but also demonstrate that the transcriptional activities of Pax3 and KAP1 are intimately linked to their acetylation status. ..
  19. Iwasaki S, Kobayashi M, Yoda M, Sakaguchi Y, Katsuma S, Suzuki T, et al. Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes. Mol Cell. 2010;39:292-9 pubmed publisher
    ..Our data suggest that the chaperone machinery may serve as the driving force for the RISC assembly pathway. ..
  20. Zheng G, Peng F, Ding R, Yu Y, Ouyang Y, Chen Z, et al. Identification of proteins responsible for the multiple drug resistance in 5-fluorouracil-induced breast cancer cell using proteomics analysis. J Cancer Res Clin Oncol. 2010;136:1477-88 pubmed publisher
    ..These findings may provide theoretical support for the prediction of chemotherapeutic response and reverse of MDR. ..
  21. Rao S, Sharma J, Maity R, Jana N. Co-chaperone CHIP stabilizes aggregate-prone malin, a ubiquitin ligase mutated in Lafora disease. J Biol Chem. 2010;285:1404-13 pubmed publisher
    ..All together, our results suggest that malin is unstable, and the aggregate-prone protein and co-chaperone CHIP can modulate its stability. ..
  22. Saitoh H, Dasso M. The RCC1 protein interacts with Ran, RanBP1, hsc70, and a 340-kDa protein in Xenopus extracts. J Biol Chem. 1995;270:10658-63 pubmed
    ..The fourth protein is novel and has a molecular mass of 340 kDa. In this report, we discuss a preliminary characterization of the interactions between these proteins. ..
  23. Nirde P, Derocq D, Maynadier M, Chambon M, Basile I, Gary Bobo M, et al. Heat shock cognate 70 protein secretion as a new growth arrest signal for cancer cells. Oncogene. 2010;29:117-27 pubmed publisher
    ..These results suggest a new role of this secreted hsc70 chaperone in cell proliferation that might account for the higher tumor growth of cancer cells overexpressing cath D. ..
  24. Minami Y, Kawasaki H, Minami M, Tanahashi N, Tanaka K, Yahara I. A critical role for the proteasome activator PA28 in the Hsp90-dependent protein refolding. J Biol Chem. 2000;275:9055-61 pubmed
    ..Kinetics of substrate binding support the idea that PA28 acts as the molecular link between the Hsp90-dependent capture of unfolded proteins and the Hsc70- and ATP-dependent refolding process. ..
  25. Qiao L, Zhang J. Inhibition of lysosomal functions reduces proteasomal activity. Neurosci Lett. 2009;456:15-9 pubmed publisher
    ..Inhibition of lysosomal or proteasomal activities led to higher levels of chaperone heat shock cognate protein Hsc70, suggesting an attempt to compensate protein degradation deficiency by enhancing chaperone-mediated autophagy. ..
  26. Witt S. The Fink blueprint for Hsp70/Hsc70 molecular chaperones. Curr Protein Pept Sci. 2009;10:424-31 pubmed
    ..As of the summer of 2008, his article had received 297 citations. I discuss here the influence Tony's iconic article has had on the chaperone field. ..
  27. Dokladny K, Lobb R, Wharton W, Ma T, Moseley P. LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-kappaB. Cell Stress Chaperones. 2010;15:153-63 pubmed publisher
    ..We conclude that the effects of heat stress-induced increase in HSP70 protein expression on LPS-induced cytokine elaboration in whole animals can be reproduced by the actions of a single gene product. ..
  28. Leung S, Hightower L. A 16-kDa protein functions as a new regulatory protein for Hsc70 molecular chaperone and is identified as a member of the Nm23/nucleoside diphosphate kinase family. J Biol Chem. 1997;272:2607-14 pubmed
    ..Pc complex. In addition, two nonconservative amino acid subsitutions were found near the amino terminus of p16. Therefore, p16 may be a unique Nm23/NDP kinase that functions as an accessory protein for cytosolic Hsc70 in eukaryotes. ..
  29. Guinez C, Mir A, Martin N, Leprince D, Michalski J, Vergoten G, et al. Arginine 469 is a pivotal residue for the Hsc70-GlcNAc-binding property. Biochem Biophys Res Commun. 2010;400:537-42 pubmed publisher
    ..SPORT6 vector and we showed that the mutation R469A decreased the GlcNAc-binding property of the chaperone of around 70%. This is the first work reporting the localization of the GlcNAc-binding domain of a member of the HSP70 family. ..
  30. Gutierrez M, Isa P, Sánchez San Martín C, Pérez Vargas J, Espinosa R, Arias C, et al. Different rotavirus strains enter MA104 cells through different endocytic pathways: the role of clathrin-mediated endocytosis. J Virol. 2010;84:9161-9 pubmed publisher
    ..The inhibition of other endocytic mechanisms, such as macropinocytosis or caveola-mediated uptake, had no effect on the internalization of the rotavirus strains tested here. ..
  31. Jiang R, Gao B, Prasad K, Greene L, Eisenberg E. Hsc70 chaperones clathrin and primes it to interact with vesicle membranes. J Biol Chem. 2000;275:8439-47 pubmed
    ..We propose that Hsc70 not only uncoats clathrin but also chaperones it to prevent it from inappropriately polymerizing in the cell cytosol and primes it to reform clathrin-coated pits. ..
  32. Okiyoneda T, Barriere H, Bagdany M, Rabeh W, Du K, Hohfeld J, et al. Peripheral protein quality control removes unfolded CFTR from the plasma membrane. Science. 2010;329:805-10 pubmed publisher
  33. Peng Z, Fan B, Du N, Wang Y, Gao L, Li Y, et al. Small molecular compounds that inhibit hepatitis C virus replication through destabilizing heat shock cognate 70 messenger RNA. Hepatology. 2010;52:845-53 pubmed publisher
    ..IMB-DM122 showed considerable good safety in vitro as well as in vivo with no indication of harmful effect on liver and kidney functions. Hsc70 might be a new drug target and mechanism to inhibit HCV proliferation. ..
  34. Laszlo A, Fleischer I. Heat-induced perturbations of DNA damage signaling pathways are modulated by molecular chaperones. Cancer Res. 2009;69:2042-9 pubmed publisher
    ..Our results support the notion that heat-induced perturbations in the earliest events of the cellular response to ionizing radiation-induced DNA damage play a role in heat radiosensitization. ..
  35. Löffek S, Wöll S, Hohfeld J, Leube R, Has C, Bruckner Tuderman L, et al. The ubiquitin ligase CHIP/STUB1 targets mutant keratins for degradation. Hum Mutat. 2010;31:466-76 pubmed publisher
    ..Thus, modulation of the chaperone machinery using small molecules may represent a novel therapeutic strategy for dominant EBS, allowing reformation of an intact keratin cytoskeleton. ..
  36. Scott Ward T, Amaral M. Deletion of Phe508 in the first nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator increases its affinity for the heat shock cognate 70 chaperone. FEBS J. 2009;276:7097-109 pubmed publisher
    ..Moreover, we show how this surface plasmon resonance assay helps to elucidate the mechanism of action of small corrective molecules, demonstrating its potential to validate additional therapeutic compounds for CF. ..
  37. Sharp A, Cutress R, Johnson P, Packham G, Townsend P. Short peptides derived from the BAG-1 C-terminus inhibit the interaction between BAG-1 and HSC70 and decrease breast cancer cell growth. FEBS Lett. 2009;583:3405-11 pubmed publisher
    ..In conclusion, we have identified a small domain within BAG-1 which appears to play a critical role in the interaction with HSC70. ..
  38. Zhang M, Sun Z, Fu X, Chen C, Ding M. [Study on proteomics of Jurkat cells treated with the extracts from Prunella vulgaris]. Zhong Yao Cai. 2009;32:917-22 pubmed
    ..The extracts from Prunella vulgaris could inhibit the growth of Jurkat cells significantly, and lead the proteomics change of Jurkat cells, which may be related to the anti-tumor effect of the extracts from Prunella vulgaris. ..
  39. Shiota M, Kusakabe H, Izumi Y, Hikita Y, Nakao T, Funae Y, et al. Heat shock cognate protein 70 is essential for Akt signaling in endothelial function. Arterioscler Thromb Vasc Biol. 2010;30:491-7 pubmed publisher
    ..Collectively, Hsc70 plays a significant role in ECs via the phosphatidylinositol 3-kinase/Akt pathway. Hsc70 may provide the basis for the development of new therapeutic strategies for angiogenesis. ..
  40. Reddy P, Mallikarjuna G, Kaul T, Chakradhar T, Mishra R, Sopory S, et al. Molecular cloning and characterization of gene encoding for cytoplasmic Hsc70 from Pennisetum glaucum may play a protective role against abiotic stresses. Mol Genet Genomics. 2010;283:243-54 pubmed publisher
    ..coli, suggest its probable role in conferring abiotic stress tolerance to this plant...
  41. Fishelson Z, Hochman I, Greene L, Eisenberg E. Contribution of heat shock proteins to cell protection from complement-mediated lysis. Int Immunol. 2001;13:983-91 pubmed
    ..Altogether, the results suggest that the heat shock proteins hsc70 and hsp70 play a role in cell defense against complement. ..
  42. Krivoruchko A, Storey K. Regulation of the heat shock response under anoxia in the turtle, Trachemys scripta elegans. J Comp Physiol B. 2010;180:403-14 pubmed publisher
    ..s. elegans and suggest that the heat shock response is an important aspect of cytoprotection during facultative anaerobiosis, particularly with regard to underwater hibernation of turtles in cold water. ..
  43. Pinsino A, Matranga V, Trinchella F, Roccheri M. Sea urchin embryos as an in vivo model for the assessment of manganese toxicity: developmental and stress response effects. Ecotoxicology. 2010;19:555-62 pubmed publisher
  44. Alam M, Harken J, Knorn A, Elford A, Wigmore K, Ohashi P, et al. Transgenic expression of Hsc70 in pancreatic islets enhances autoimmune diabetes in response to beta cell damage. J Immunol. 2009;183:5728-37 pubmed publisher
    ..These findings suggest that an elevated content of hsc70 in cells undergoing necrotic or apoptotic cell death can increase the extent of sterile inflammation and increase the susceptibility to autoimmunity. ..
  45. Gharesi Fard B, Zolghadri J, Kamali Sarvestani E. Proteome differences of placenta between pre-eclampsia and normal pregnancy. Placenta. 2010;31:121-5 pubmed publisher
  46. de Andrade A, Siviero F, Rezende Teixeira P, Santelli R, Machado Santelli G. Molecular characterization of a putative heat shock protein cognate gene in Rhynchosciara americana. Chromosome Res. 2009;17:935-45 pubmed publisher
    ..In situ hybridization of polytene chromosomes showed that the Rahsc70 gene is located near the C3 DNA puff. The cellular localization of Hsc70 protein showed this protein in the cytoplasm and in the nucleus. ..
  47. Requena D, Parra L, Baust T, Quiroz M, Leak R, Garcia Olivares J, et al. The molecular chaperone Hsc70 interacts with the vesicular monoamine transporter-2. J Neurochem. 2009;110:581-94 pubmed publisher
    ..Finally, a purified Hsc70 fragment that binds VMAT2 was sufficient to inhibit VMAT2 activity in synaptic vesicles. Our results suggest an important role for Hsc70 in VMAT2 function and regulation. ..
  48. Terada K, Oike Y. Multiple molecules of Hsc70 and a dimer of DjA1 independently bind to an unfolded protein. J Biol Chem. 2010;285:16789-97 pubmed publisher
    ..Instead, these results suggest the importance of the bivalent binding of DjA1 dimer that limits unfavorable transitions of substrate conformations in protein folding. ..
  49. Chu Y, Dodiya H, Aebischer P, Olanow C, Kordower J. Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions. Neurobiol Dis. 2009;35:385-98 pubmed publisher
  50. Xing Y, Böcking T, Wolf M, Grigorieff N, Kirchhausen T, Harrison S. Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly. EMBO J. 2010;29:655-65 pubmed publisher
    ..Accumulation of the local strain thus imposed at multiple vertices can then lead to disassembly. ..
  51. Lalouette L, Renault D, Ravaux J, Siaussat D. Effects of cold-exposure and subsequent recovery on cellular proliferation with influence of 20-hydroxyecdysone in a lepidopteran cell line (IAL-PID2). Comp Biochem Physiol A Mol Integr Physiol. 2010;155:407-14 pubmed publisher
  52. Gancz D, Fishelson Z. Cancer resistance to complement-dependent cytotoxicity (CDC): Problem-oriented research and development. Mol Immunol. 2009;46:2794-800 pubmed publisher
    ..It is conceivable that the therapeutic capacity of anti-cancer antibodies will be amplified once combined with a reagent that sensitizes the cancer cells to CDC. ..
  53. Schirmbeck R, Bohm W, Reimann J. Stress protein (hsp73)-mediated, TAP-independent processing of endogenous, truncated SV40 large T antigen for Db-restricted peptide presentation. Eur J Immunol. 1997;27:2016-23 pubmed
    ..The described data indicate that a pool of post-Golgi Db molecules is available for 2-3 h in TAP-deficient transfectants for loading with peptides released during endolysosomal processing of hsp73-associated, endogenous antigen. ..