Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Biol Cell
2004 Dec 01;1512:5623-34. doi: 10.1091/mbc.e04-07-0598.
Show Gene links
Show Anatomy links
Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1.
???displayArticle.abstract???
Progression through mitosis requires activation of cyclin B/Cdk1 and its downstream targets, including Polo-like kinase and the anaphase-promoting complex (APC), the ubiquitin ligase directing degradation of cyclins A and B. Recent evidence shows that APC activation requires destruction of the APC inhibitor Emi1. In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to recruit the SCF(betaTrCP) ubiquitin ligase, causing Emi1 destruction and allowing progression beyond prometaphase, but the kinases directing this phosphorylation remain undefined. We show here that the polo-like kinase Plk1 is strictly required for Emi1 destruction and that overexpression of Plk1 is sufficient to trigger Emi1 destruction. Plk1 stimulates Emi1 phosphorylation, betaTrCP binding, and ubiquitination in vitro and cyclin B/Cdk1 enhances these effects. Plk1 binds to Emi1 in mitosis and the two proteins colocalize on the mitotic spindle poles, suggesting that Plk1 may spatially control Emi1 destruction. These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase.
Abrieu,
The Polo-like kinase Plx1 is a component of the MPF amplification loop at the G2/M-phase transition of the cell cycle in Xenopus eggs.
1998, Pubmed,
Xenbase
Abrieu,
The Polo-like kinase Plx1 is a component of the MPF amplification loop at the G2/M-phase transition of the cell cycle in Xenopus eggs.
1998,
Pubmed
,
Xenbase Bahassi,
Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation.
2004,
Pubmed Barr,
Polo-like kinases and the orchestration of cell division.
2004,
Pubmed Cheng,
The crystal structure of the human polo-like kinase-1 polo box domain and its phospho-peptide complex.
2003,
Pubmed Deak,
Mutations in mákos, a Drosophila gene encoding the Cdc27 subunit of the anaphase promoting complex, enhance centrosomal defects in polo and are suppressed by mutations in twins/aar, which encodes a regulatory subunit of PP2A.
2003,
Pubmed den Elzen,
Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase.
2001,
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 Donzelli,
Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation.
2004,
Pubmed Elia,
The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain.
2003,
Pubmed
,
Xenbase Elia,
Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates.
2003,
Pubmed Erikson,
A feedback loop in the polo-like kinase activation pathway.
2004,
Pubmed
,
Xenbase Freed,
Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle.
1999,
Pubmed
,
Xenbase Fuchs,
The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer.
2004,
Pubmed Golan,
The cyclin-ubiquitin ligase activity of cyclosome/APC is jointly activated by protein kinases Cdk1-cyclin B and Plk.
2002,
Pubmed Golsteyn,
Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function.
1995,
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 Hart,
The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell.
1999,
Pubmed Hershko,
Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2.
1994,
Pubmed Hsu,
E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1).
2002,
Pubmed
,
Xenbase Jackman,
Active cyclin B1-Cdk1 first appears on centrosomes in prophase.
2003,
Pubmed Jackson,
Early events in DNA replication require cyclin E and are blocked by p21CIP1.
1995,
Pubmed
,
Xenbase Jang,
Functional studies on the role of the C-terminal domain of mammalian polo-like kinase.
2002,
Pubmed Jin,
SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase.
2003,
Pubmed Kelm,
Cell cycle-regulated phosphorylation of the Xenopus polo-like kinase Plx1.
2002,
Pubmed
,
Xenbase King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase Kotani,
PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression.
1998,
Pubmed Kraft,
Mitotic regulation of the human anaphase-promoting complex by phosphorylation.
2003,
Pubmed Kramer,
Mitotic regulation of the APC activator proteins CDC20 and CDH1.
2000,
Pubmed
,
Xenbase 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 Lee,
Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1.
1995,
Pubmed Lew,
The spindle assembly and spindle position checkpoints.
2003,
Pubmed Liu,
The polo box is required for multiple functions of Plx1 in mitosis.
2004,
Pubmed
,
Xenbase Liu,
Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.
2002,
Pubmed
,
Xenbase Llamazares,
polo encodes a protein kinase homolog required for mitosis in Drosophila.
1991,
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 Montagnoli,
Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.
1999,
Pubmed Moshe,
Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome.
2004,
Pubmed
,
Xenbase Mundt,
On the regulation and function of human polo-like kinase 1 (PLK1): effects of overexpression on cell cycle progression.
1997,
Pubmed Murray,
Recycling the cell cycle: cyclins revisited.
2004,
Pubmed Nakajima,
Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate.
2003,
Pubmed
,
Xenbase Neef,
Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis.
2003,
Pubmed Nigg,
Mitotic kinases as regulators of cell division and its checkpoints.
2001,
Pubmed Orlicky,
Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase.
2003,
Pubmed Qian,
Activated polo-like kinase Plx1 is required at multiple points during mitosis in Xenopus laevis.
1998,
Pubmed
,
Xenbase Reimann,
Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins.
2001,
Pubmed
,
Xenbase Reimann,
Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.
2001,
Pubmed
,
Xenbase Reimann,
Emi1 is required for cytostatic factor arrest in vertebrate eggs.
2002,
Pubmed
,
Xenbase Rudner,
Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex.
2000,
Pubmed Shou,
Cdc5 influences phosphorylation of Net1 and disassembly of the RENT complex.
2002,
Pubmed
,
Xenbase Shteinberg,
Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20.
1999,
Pubmed Sudakin,
The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
1995,
Pubmed Sunkel,
polo, a mitotic mutant of Drosophila displaying abnormal spindle poles.
1988,
Pubmed van Vugt,
Polo-like kinase-1 is required for bipolar spindle formation but is dispensable for anaphase promoting complex/Cdc20 activation and initiation of cytokinesis.
2004,
Pubmed Waizenegger,
Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase.
2000,
Pubmed
,
Xenbase Watanabe,
M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP.
2004,
Pubmed Winston,
The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.
1999,
Pubmed Wu,
Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase.
2003,
Pubmed Yarm,
Plk phosphorylation regulates the microtubule-stabilizing protein TCTP.
2002,
Pubmed Yaron,
Identification of the receptor component of the IkappaBalpha-ubiquitin ligase.
1998,
Pubmed
