Tyrosine phosphorylation controls PCNA function through protein stability.

The proliferating cell nuclear antigen (PCNA) is an essential protein for DNA replication and damage repair. How its function is controlled remains an important question. Here, we show that the chromatin-bound PCNA protein is phosphorylated on Tyr 211, which is required for maintaining its function on chromatin and is dependent ...
on the tyrosine kinase activity of EGF receptor (EGFR) in the nucleus. Phosphorylation on Tyr 211 by EGFR stabilizes chromatin-bound PCNA protein and associated functions. Consistently, increased PCNA Tyr 211 phosphorylation coincides with pronounced cell proliferation, and is better correlated with poor survival of breast cancer patients, as well as nuclear EGFR in tumours, than is the total PCNA level. These results identify a novel nuclear mechanism linking tyrosine kinase receptor function with the regulation of the PCNA sliding clamp.
Mesh Terms:
Cell Nucleus, Cell Proliferation, Chromatin, DNA Repair, DNA Replication, Hela Cells, Humans, Phosphorylation, Phosphotyrosine, Proliferating Cell Nuclear Antigen, Protein Binding, Receptor, Epidermal Growth Factor, Thermodynamics
Nat. Cell Biol.
Date: Dec. 01, 2006
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