title: Ydj1 protects nascent protein kinases from degradation and controls the rate of their maturation.
abstract: Ydj1 is a Saccharomyces cerevisiae Hsp40 molecular chaperone that functions with Hsp70 to promote polypeptide folding. We identified Ydj1 as being important for maintaining steady-state levels of protein kinases after screening several chaperones and cochaperones in gene deletion mutant strains. Pulse-chase analyses revealed that a portion of Tpk2 kinase was degraded shortly after synthesis in a ydj1Delta mutant, while the remainder was capable of maturing but with reduced kinetics compared to the wild type. Cdc28 maturation was also delayed in the ydj1Delta mutant strain. Ydj1 protects nascent kinases in different contexts, such as when Hsp90 is inhibited with geldanamycin or when CDC37 is mutated. The protective function of Ydj1 is due partly to its intrinsic chaperone function, but this is minor compared to the protective effect resulting from its interaction with Hsp70. SIS1, a type II Hsp40, was unable to suppress defects in kinase accumulation in the ydj1Delta mutant, suggesting some specificity in Ydj1 chaperone action. However, analysis of chimeric proteins that contained the chaperone modules of Ydj1 or Sis1 indicated that Ydj1 promotes kinase accumulation independently of its client-binding specificity. Our results suggest that Ydj1 can both protect nascent chains against degradation and control the rate of kinase maturation.
authors.affiliation: Department of Biology, City College New York, Convent Avenue at 138th Street, New York, NY 10031, USA.
authors.forename: Atin K
authors.initials: AK
authors.lastname: Mandal
authors.forename: Nadinath B
authors.initials: NB
authors.lastname: Nillegoda
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chen
authors.forename: Avrom J
authors.initials: AJ
authors.lastname: Caplan
mesh_terms: D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D004795:Enzyme Stability; D017353:Gene Deletion; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012995:Solubility
chemical_list: C513270:CDC37 protein, S cerevisiae; D018797:Cell Cycle Proteins; D050956:HSP40 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C070319:YDJ1 protein, S cerevisiae; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C457179:TPK2 protein, S cerevisiae; D017489:CDC28 Protein Kinase, S cerevisiae