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Pin1 stabilizes Emi1 during G2 phase by preventing its association with SCF(betatrcp)
Cyril Bernis1, Suzanne Vigneron, Andrew Burgess
1Centre de Recherche de Biochimie Macromoléculaire, CNRS FRE 2593, 1919 Route de Mende, 34293 Montpellier cedex 5, France.
Abstract:
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.
Insights
Pin1 stabilizes early mitotic inhibitor 1 (Emi1) by preventing its degradation during G2 phase. This Pin1-dependent stabilization of Emi1 is crucial for cell cycle progression into S and M phases.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Early mitotic inhibitor 1 (Emi1) is essential for initiating S and M phases by promoting cyclin A and cyclin B accumulation.
- Emi1 degradation is typically mediated by SCF(beta-TrCP) and cyclin A/cdk, yet Emi1 remains stable during G2 when these factors are active.
Purpose of the Study:
- To identify the mechanism stabilizing Emi1 during G2 phase.
- To elucidate the role of Pin1 in regulating Emi1 stability and cell cycle progression.
Main Methods:
- Investigated Emi1-Pin1 interactions in vitro and in vivo.
- Utilized XL2 cells to study Emi1-Pin1 binding during G2 phase.
- Examined the effect of Pin1 on Emi1 association with SCF(beta-TrCP).
Main Results:
- Identified Pin1 as a novel regulator that stabilizes Emi1.
- Demonstrated that Pin1 binds to Emi1 in an isomerization-dependent manner.
- Showed that Pin1 binding prevents Emi1's association with SCF(beta-TrCP), thereby inhibiting its degradation during G2.
- Confirmed Emi1-Pin1 interaction in vivo during G2 phase.
Conclusions:
- Pin1 stabilizes Emi1 during G2 phase by preventing its degradation.
- Pin1-dependent Emi1 stabilization is critical for the accumulation of cyclin A and cyclin B.
- This mechanism facilitates entry into S and M phases of the cell cycle.
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