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Updated: Jan 18, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression
Andrew W Truman1, Kolbrun Kristjansdottir, Donald Wolfgeher
1Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
Heat shock protein 70 (Hsp70) phosphorylation by cyclin-dependent kinases (CDKs) controls G1 cyclin stability and cell cycle progression. This mechanism, conserved in humans, regulates growth by modulating cyclin abundance and activity.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Hsp70 chaperones are essential proteins regulating cellular functions.
- Their activity is modulated by expression, isoform, and cochaperones.
Purpose of the Study:
- To investigate a novel regulatory mechanism of Hsp70 function.
- To explore the role of Hsp70 phosphorylation in cell cycle control.
Main Methods:
- Phosphorylation site analysis in budding yeast Ssa1.
- Investigating interactions between Ssa1, Ydj1, and Cln3.
- Studying the effects of CDK Pho85 and Cdk1 on Ssa1 phosphorylation and Cln3 stability.
- Examining conserved phosphorylation in human Hsc70 and Cyclin D1.
Main Results:
- Phosphorylation of Ssa1 at T36 by CDKs alters cochaperone and client interactions.
- T36 phosphorylation displaces Ydj1, enabling Ssa1 to bind and degrade G1 cyclin Cln3.
- Stress and mitotic CDKs (Pho85, Cdk1) regulate Cln3 stability via Ssa1 phosphorylation.
- CDK-dependent phosphorylation of human Hsc70 T38 affects Cyclin D1 stability.
Conclusions:
- Hsp70 acts as a signal transducer in cell growth control.
- CDK-mediated Hsp70 phosphorylation regulates G1 cyclin abundance and activity.
- This phosphorylation mechanism is conserved from yeast to humans.
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