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CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression
- Source :
- Cell
- Publication Year :
- 2012
- Publisher :
- Elsevier, 2012.
-
Abstract
- Summary 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.<br />Graphical Abstract Highlights ► First demonstration of regulation of Hsp70 function through CDK phosphorylation ► Cdk1 and Pho85 phosphorylate Ssa1 to regulate binding to Cln3 and Cln3 destruction ► Cln3 degradation requires both Cln3 phosphorylation and Cln3 binding to Ssa1 ► CDK-mediated phosphorylation of Hsc70 targets Cyclin D1 abundance and activity<br />Cyclin-dependent kinases directly phosphorylate yeast Hsp70 to enhance its interaction with Cyclin 3, triggering its destruction and the G1/S checkpoint, showing that chaperone proteins can act as signal transducers during cell-cycle progression.
- Subjects :
- Saccharomyces cerevisiae Proteins
Cyclin D
Cyclin A
Saccharomyces cerevisiae
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Phosphorylation cascade
03 medical and health sciences
Cyclin D1
Cyclin-dependent kinase
Cyclins
Humans
HSP70 Heat-Shock Proteins
Phosphorylation
030304 developmental biology
Cell Proliferation
Adenosine Triphosphatases
0303 health sciences
Cyclin-dependent kinase 1
Biochemistry, Genetics and Molecular Biology(all)
030302 biochemistry & molecular biology
Cell Cycle
HSC70 Heat-Shock Proteins
3. Good health
Cell biology
HEK293 Cells
Biochemistry
biology.protein
Cyclin-dependent kinase complex
Cyclin A2
Subjects
Details
- Language :
- English
- ISSN :
- 00928674
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....ee177785b27712af8713104c55715d32