1-s2.0-S0092867412013645-main.pdf (1.37 MB)
CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression
journal contribution
posted on 2023-06-08, 14:13 authored by Andrew W Truman, Kolbrun Kristjansdottir, Donald Wolfgeher, Naushaba Hasin, Sigrun Polier, Hong Zhang, Sarah Perrett, Chrisostomos ProdromouChrisostomos Prodromou, Gary W Jones, Stephen J KronIn 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.
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Publication status
- Published
File Version
- Published version
Journal
CellISSN
0092-8674Publisher
ElsevierExternal DOI
Issue
6Volume
151Page range
1308-1318Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2013-01-15First Open Access (FOA) Date
2019-03-27First Compliant Deposit (FCD) Date
2019-07-01Usage metrics
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