title: Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation.
abstract: Cdc37 is a molecular chaperone that functions with Hsp90 to promote protein kinase folding. Analysis of 65 Saccharomyces cerevisiae protein kinases ( approximately 50% of the kinome) in a cdc37 mutant strain showed that 51 had decreased abundance compared with levels in the wild-type strain. Several lipid kinases also accumulated in reduced amounts in the cdc37 mutant strain. Results from our pulse-labeling studies showed that Cdc37 protects nascent kinase chains from rapid degradation shortly after synthesis. This degradation phenotype was suppressed when cdc37 mutant cells were grown at reduced temperatures, although this did not lead to a full restoration of kinase activity. We propose that Cdc37 functions at distinct steps in kinase biogenesis that involves protecting nascent chains from rapid degradation followed by its folding function in association with Hsp90. Our studies demonstrate that Cdc37 has a general role in kinome biogenesis.
authors.affiliation: Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Atin K
authors.initials: AK
authors.lastname: Mandal
authors.forename: Paul
authors.initials: P
authors.lastname: Lee
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chen
authors.forename: Nadinath
authors.initials: N
authors.lastname: Nillegoda
authors.forename: Alana
authors.initials: A
authors.lastname: Heller
authors.forename: Susan
authors.initials: S
authors.lastname: DiStasio
authors.forename: Handy
authors.initials: H
authors.lastname: Oen
authors.forename: Jacob
authors.initials: J
authors.lastname: Victor
authors.forename: Devi M
authors.initials: DM
authors.lastname: Nair
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Brodsky
authors.forename: Avrom J
authors.initials: AJ
authors.lastname: Caplan
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D016681:Genome, Fungal; D050356:Lipid Metabolism; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C513270:CDC37 protein, S cerevisiae; D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins