Pin1 stabilizes Emi1 during G2 phase by preventing its association with SCF(betatrcp).
The anaphase-promoting complex (APC) early mitotic inhibitor 1 (Emi1) is required to induce S- and M-phase entries by stimulating the accumulation of cyclin A and cyclin B through APC(Cdh1/cdc20) inhibition. In this report, we show that Emi1 proteolysis can be induced by cyclin A/cdk (cdk for cyclin-dependent kinase). Paradoxically, Emi1 is stable during G2 phase, when cyclin A/cdk, Plx1 and SCF(betatrcp) (SCF for Skp1-Cul1-Fbox protein)--which play a role in its degradation--are active. Here, we identify Pin1 as a new regulator of Emi1 that induces Emi1 stabilization by preventing its association with SCF(betatrcp). We show that Pin1 binds to Emi1 and prevents its association with betatrcp in an isomerization-dependent pathway. We also show that Emi1-Pin1 binding is present in vivo in XL2 cells during G2 phase and that this association protects Emi1 from being degraded during this phase of the cell cycle. We propose that S- and M-phase entries are mediated by the accumulation of cyclin A and cyclin B through a Pin1-dependent stabilization of Emi1 during G2.
Bernis
Cyril
C
Centre de Recherche de Biochimie Macromoléculaire, CNRS FRE 2593, 1919 Route de Mende, 34293 Montpellier cedex 5, France.
Vigneron
Suzanne
S
Burgess
Andrew
A
Labbé
Jean-Claude
JC
Fesquet
Didier
D
Castro
Anna
A
Lorca
Thierry
T
D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002457:Cell Extracts / Q000737:chemistry; D019925:Cyclin A / Q000378:metabolism / Q000494:pharmacology; D019926:Cyclin B / Q000378:metabolism / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000494:pharmacology; D016195:G2 Phase; D006801:Humans; D047468:Immunoprecipitation; D008938:Mitosis; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D002457:Cell Extracts; D019925:Cyclin A; D019926:Cyclin B; C429107:FBXO5 protein, Xenopus; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D029867:Xenopus Proteins; D044844:beta-Transducin Repeat-Containing Proteins; D018844:Cyclin-Dependent Kinases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase