CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression

Truman, Andrew W, Kristjansdottir, Kolbrun, Wolfgeher, Donald, Hasin, Naushaba, Polier, Sigrun, Zhang, Hong, Perrett, Sarah, Prodromou, Chrisostomos, Jones, Gary W and Kron, Stephen J (2012) CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression. Cell, 151 (6). pp. 1308-1318. ISSN 0092-8674

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science
Depositing User: Deeptima Massey
Date Deposited: 15 Jan 2013 15:45
Last Modified: 19 Jun 2013 10:07
URI: http://sro.sussex.ac.uk/id/eprint/43464
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