title: CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression.
abstract: In budding yeast, the essential functions of Hsp70 chaperones Ssa1-4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity.
authors.affiliation: Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Truman
authors.forename: Kolbrun
authors.initials: K
authors.lastname: Kristjansdottir
authors.forename: Donald
authors.initials: D
authors.lastname: Wolfgeher
authors.forename: Naushaba
authors.initials: N
authors.lastname: Hasin
authors.forename: Sigrun
authors.initials: S
authors.lastname: Polier
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Sarah
authors.initials: S
authors.lastname: Perrett
authors.forename: Chrisostomos
authors.initials: C
authors.lastname: Prodromou
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jones
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kron
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D057809:HEK293 Cells; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D019938:Cyclin D1; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae