Reference - PMID:15629716 - Inactivation of the Cdc25 phosphatase by the stress-activated Srk1 kinase in fission yeast.

Reference summary

PubMed ID

PMID:15629716

Title

Inactivation of the Cdc25 phosphatase by the stress-activated Srk1 kinase in fission yeast.

Authors

López-Avilés S, Grande M, González M, Helgesen AL, Alemany V, Sanchez-Piris M, Bachs O, Millar JB, Aligue R

Citation

Mol Cell 2005 Jan 07;17(1):49-59

Publication year

2005

Abstract

The mechanisms by which environmental stress regulates cell cycle progression are poorly understood. In fission yeast, we show that Srk1 kinase, which associates with the stress-activated p38/Sty1 MAP kinase, regulates the onset of mitosis by inhibiting the Cdc25 phosphatase. Srk1 is periodically active in G2, and its overexpression causes cell cycle arrest in late G2 phase, whereas cells lacking srk1 enter mitosis prematurely. We find that Srk1 interacts with and phosphorylates Cdc25 at the same sites phosphorylated by the Chk1 and Cds1 (Chk2) kinases and that this phosphorylation is necessary for Srk1 to delay mitotic entry. Phosphorylation by Srk1 causes Cdc25 to bind to Rad24, a 14-3-3 protein family member, and accumulation of Cdc25 in the cytoplasm. However, Srk1 does not regulate Cdc25 in response to replication arrest or DNA damage but, rather, during a normal cell cycle and in response to nongenotoxic environmental stress.

Annotation