The xenopus Suc1/Cks protein promotes the phosphorylation of G(2)/M regulators.
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.
Patra
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Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
Wang
S X
SX
Kumagai
A
A
Dunphy
W G
WG
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins; D019926:Cyclin B / Q000378:metabolism; D005260:Female; D005656:Fungal Proteins / Q000502:physiology*; D016195:G2 Phase; D008938:Mitosis; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D019696:Peptidylprolyl Isomerase / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D020687:cdc25 Phosphatases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C081185:CKS1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D005656:Fungal Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C051655:Suc1 protein, S pombe; D029867:Xenopus Proteins; C095970:MYT1 kinase, Xenopus; C530005:WEE1 protein, Xenopus; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases; C000606845:ESS1 protein, S cerevisiae; D019696:Peptidylprolyl Isomerase