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Proc Natl Acad Sci U S A
2004 May 25;10121:7937-42. doi: 10.1073/pnas.0402442101.
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Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome.
Moshe Y
,
Boulaire J
,
Pagano M
,
Hershko A
.
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Early mitotic inhibitor 1 (Emi1) inhibits the activity of the anaphase promoting complex/cyclosome (APC/C), which is a multisubunit ubiquitin ligase that targets mitotic regulators for degradation in exit from mitosis. Levels of Emi1 oscillate in the cell cycle: it accumulates in the S phase and is rapidly degraded in prometaphase. The degradation of Emi1 in early mitosis is necessary for the activation of APC/C in late mitosis. Previous studies have shown that Emi1 is targeted for degradation in mitosis by a Skp1-Cullin1 F-box protein (SCF) ubiquitin ligase complex that contains the F-box protein beta-TrCP. As with other substrates of SCF(beta-TrCP), the phosphorylation of Emi1 on a DSGxxS sequence is required for this process. However, the protein kinase(s) involved has not been identified. We find that Polo-like kinase 1 (Plk1), a protein kinase that accumulates in mitosis, markedly stimulates the ligation of Emi1 to ubiquitin by purified SCF(beta-TrCP). Cdk1-cyclin B, another major mitotic protein kinase, has no influence on this process by itself but stimulates the action of Plk1 at low, physiological concentrations. Plk1 phosphorylates serine residues in the DSGxxS sequence of Emi1, as suggested by the reduced phosphorylation of a derivative in which the two serines were mutated to nonphosphorylatable amino acids. Transfection with an small interfering RNA duplex directed against Plk1 caused the accumulation of Emi1 in mitotically arrested HeLa cells. It is suggested that phosphorylation of Emi1 by Plk1 is involved in its degradation in mitosis.
Amit,
Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.
2002, Pubmed
Amit,
Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.
2002,
Pubmed
Bornstein,
Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase.
2003,
Pubmed
Descombes,
The polo-like kinase Plx1 is required for M phase exit and destruction of mitotic regulators in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Dong,
Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A.
1997,
Pubmed
Elia,
Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates.
2003,
Pubmed
Elia,
The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain.
2003,
Pubmed
,
Xenbase
Golan,
The cyclin-ubiquitin ligase activity of cyclosome/APC is jointly activated by protein kinases Cdk1-cyclin B and Plk.
2002,
Pubmed
Guardavaccaro,
Oncogenic aberrations of cullin-dependent ubiquitin ligases.
2004,
Pubmed
Guardavaccaro,
Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo.
2003,
Pubmed
Harper,
The anaphase-promoting complex: it's not just for mitosis any more.
2002,
Pubmed
Hsu,
E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1).
2002,
Pubmed
,
Xenbase
King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase
Kraft,
Mitotic regulation of the human anaphase-promoting complex by phosphorylation.
2003,
Pubmed
Kumagai,
Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts.
1996,
Pubmed
,
Xenbase
Lahav-Baratz,
Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase.
1995,
Pubmed
Laney,
Substrate targeting in the ubiquitin system.
1999,
Pubmed
Liu,
Activation of Cdc2/cyclin B and inhibition of centrosome amplification in cells depleted of Plk1 by siRNA.
2002,
Pubmed
Maniatis,
A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways.
1999,
Pubmed
Margottin-Goguet,
Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase.
2003,
Pubmed
,
Xenbase
Nakajima,
Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate.
2003,
Pubmed
,
Xenbase
Nigg,
Polo-like kinases: positive regulators of cell division from start to finish.
1998,
Pubmed
Peters,
The anaphase-promoting complex: proteolysis in mitosis and beyond.
2002,
Pubmed
Reimann,
Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.
2001,
Pubmed
,
Xenbase
Reimann,
Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins.
2001,
Pubmed
,
Xenbase
Rudner,
Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex.
2000,
Pubmed
Scacheri,
Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells.
2004,
Pubmed
Semizarov,
Specificity of short interfering RNA determined through gene expression signatures.
2003,
Pubmed
Shteinberg,
Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20.
1999,
Pubmed
Spänkuch-Schmitt,
Effect of RNA silencing of polo-like kinase-1 (PLK1) on apoptosis and spindle formation in human cancer cells.
2002,
Pubmed
Sudakin,
The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
1995,
Pubmed
Yarm,
Plk phosphorylation regulates the microtubule-stabilizing protein TCTP.
2002,
Pubmed
Yudkovsky,
Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint.
2000,
Pubmed