title: Cofactor-induced modulation of the functional specificity of the molecular chaperone Hsc70.
abstract: Molecular chaperones differ in their ability to stabilize nonnative polypeptides and to mediate protein folding, defining 'holding' and 'folding' systems. Here we show that the mammalian cytosolic and nuclear chaperone Hsc70 can act as both, as a 'holding' and a 'folding' system, depending on the chaperone cofactors which associate with Hsc70. In conjunction with the cofactor Hsp40, Hsc70 stabilizes heat-denatured firefly luciferase. The stabilizing activity turns into a folding activity in the additional presence of the Hsc70-interacting protein Hip. In contrast, the cofactor BAG-1 abrogates the 'holding' function of the Hsc70/Hsp40 system and blocks the action of Hip on Hsc70. Our study sheds light on the molecular mechanisms that determine the functional specificity of Hsc70 in the mammalian cell.
authors.affiliation: ZMBH, Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lüders
authors.forename: J
authors.initials: J
authors.lastname: Demand
authors.forename: S
authors.initials: S
authors.lastname: Schönfelder
authors.forename: M
authors.initials: M
authors.lastname: Frien
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: J
authors.initials: J
authors.lastname: Höhfeld
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D011489:Protein Denaturation; D017510:Protein Folding; D051381:Rats; D013379:Substrate Specificity; D014157:Transcription Factors
chemical_list: C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C494647:DNAJB1 protein, human; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006360:Heat-Shock Proteins; C105426:Hip chaperone; C494373:Hspa8 protein, rat; D018832:Molecular Chaperones; D014157:Transcription Factors; D008156:Luciferases; D000251:Adenosine Triphosphatases