Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1.

Cell | Jan 27, 2006

http://www.ncbi.nlm.nih.gov/pubmed/16439210

The anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 controls progression to S phase and mitosis by stabilizing key APC/C ubiquitination substrates, including cyclin A. Examining Emi1 binding proteins, we identified the Evi5 oncogene as a regulator of Emi1 accumulation. Evi5 antagonizes SCF(betaTrCP)-dependent Emi1 ubiquitination and destruction by binding to a site adjacent to Emi1's DSGxxS degron and blocking both degron phosphorylation by Polo-like kinases and subsequent betaTrCP binding. Thus, Evi5 functions as a stabilizing factor maintaining Emi1 levels in S/G2 phase. Evi5 protein accumulates in early G1 following Plk1 destruction and is degraded in a Plk1- and ubiquitin-dependent manner in early mitosis. Ablation of Evi5 induces precocious degradation of Emi1 by the Plk/SCF(betaTrCP) pathway, causing premature APC/C activation; cyclin destruction; cell-cycle arrest; centrosome overduplication; and, finally, mitotic catastrophe. We propose that the balance of Evi5 and Polo-like kinase activities determines the timely accumulation of Emi1 and cyclin, ensuring mitotic fidelity.

Pubmed ID: 16439210 RIS Download

Mesh terms: Anaphase | Anaphase-Promoting Complex-Cyclosome | Animals | Cell Cycle | Cell Cycle Proteins | Cell Line | Cyclin A | F-Box Proteins | HeLa Cells | Humans | Interphase | Models, Biological | Nuclear Proteins | Phosphorylation | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | SKP Cullin F-Box Protein Ligases | Two-Hybrid System Techniques | Ubiquitin-Protein Ligase Complexes | Xenopus

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA09302
  • Agency: NIGMS NIH HHS, Id: R01 GM060439
  • Agency: NIGMS NIH HHS, Id: R01 GM54811
  • Agency: NIGMS NIH HHS, Id: R01 GM73023

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.