The Xenopus Suc1/Cks protein promotes the phosphorylation of G2/M regulators

Debabrata Patra, Sophie X. Wang, Akiko Kumagai, William G. Dunphy

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

The entry into mitosis is controlled by Cdc2/cyclin B, also known as maturation or M-phase promoting factor (MPF). In Xenopus egg extracts, the inhibitory phosphorylations of Cdc2 on Tyr-15 and Thr-14 are controlled by the phosphatase Cdc25 and the kinases Myt1 and Wee1. At mitosis, Cdc25 is activated and Myt1 and Wee1 are inactivated through phosphorylation by multiple kinases, including Cdc2 itself. The Cdc2-associated Suc1/Cks1 protein (p9) is also essential for entry of egg extracts into mitosis, but the molecular basis of this requirement has been unknown. We find that p9 strongly stimulates the regulatory phosphorylations of Cdc25, Myt1, and Wee1 that are carried out by the Cdc2/cyclin B complex. Overexpression of the prolyl isomerase Pin1, which binds to the hyperphosphorylated forms of Cdc25, Myt1, and Wee1 found at M-phase, is known to block the initiation of mitosis in egg extracts. We have observed that Pin1 specifically antagonizes the stimulatory effect of p9 on phosphorylation of Cdc25 by Cdc2/cyclin B. This observation could explain why overexpression of Pin1 inhibits mitotic initiation. These findings suggest that p9 promotes the entry into mitosis by facilitating phosphorylation of the key upstream regulators of Cdc2.

Original languageEnglish
Pages (from-to)36839-36842
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number52
DOIs
StatePublished - Dec 24 1999

Fingerprint

Dive into the research topics of 'The Xenopus Suc1/Cks protein promotes the phosphorylation of G2/M regulators'. Together they form a unique fingerprint.

Cite this