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EMBO Rep
2007 Jan 01;81:91-8. doi: 10.1038/sj.embor.7400853.
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Pin1 stabilizes Emi1 during G2 phase by preventing its association with SCF(betatrcp).
Bernis C
,
Vigneron S
,
Burgess A
,
Labbé JC
,
Fesquet D
,
Castro A
,
Lorca T
.
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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.
Castro,
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Castro,
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Eldridge,
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,
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Furuno,
Human cyclin A is required for mitosis until mid prophase.
1999,
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Guardavaccaro,
Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo.
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Hansen,
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,
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,
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Joseph,
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Lu,
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Lu,
A human peptidyl-prolyl isomerase essential for regulation of mitosis.
1996,
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Margottin-Goguet,
Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase.
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,
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Reimann,
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2001,
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,
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Winkler,
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2000,
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,
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Wulf,
Phosphorylation-specific prolyl isomerization: is there an underlying theme?
2005,
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Yaffe,
Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism.
1997,
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van Drogen,
Ubiquitylation of cyclin E requires the sequential function of SCF complexes containing distinct hCdc4 isoforms.
2006,
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