Article

Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.

Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Cell (Impact Factor: 33.12). 07/2001; 105(5):645-55. DOI: 10.1016/S0092-8674(01)00361-0
Source: PubMed

ABSTRACT We have discovered an early mitotic inhibitor, Emi1, which regulates mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Emi1 is a conserved F box protein containing a zinc binding region essential for APC inhibition. Emi1 accumulates before mitosis and is ubiquitylated and destroyed in mitosis, independent of the APC. Emi1 immunodepletion from cycling Xenopus extracts strongly delays cyclin B accumulation and mitotic entry, whereas nondestructible Emi1 stabilizes APC substrates and causes a mitotic block. Emi1 binds the APC activator Cdc20, and Cdc20 can rescue an Emi1-induced block to cyclin B destruction. Our results suggest that Emi1 regulates progression through early mitosis by preventing premature APC activation, and may help explain the well-known delay between cyclin B/Cdc2 activation and cyclin B destruction.

0 Bookmarks
 · 
96 Views
  • Experimental and Molecular Pathology 01/2003; DOI:10.1006/S0014-4800(02)00021-7 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The appropriate timing of events that lead to chromosome segregation during mitosis and cytokinesis is essential to prevent aneuploidy, and defects in these processes can contribute to tumorigenesis. Key mitotic regulators are controlled through ubiquitylation and proteasome-mediated degradation. The APC/C (anaphase-promoting complex; also known as the cyclosome) is an E3 ubiquitin ligase that has a crucial function in the regulation of the mitotic cell cycle, particularly at the onset of anaphase and during mitotic exit. Co-activator proteins, inhibitor proteins, protein kinases and phosphatases interact with the APC/C to temporally and spatially control its activity and thus ensure accurate timing of mitotic events.
    Nature Reviews Molecular Cell Biology 01/2015; 16(2):82-94. DOI:10.1038/nrm3934 · 37.16 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Centrosome cohesion maintains centrosomes in close proximity until mitosis, when cell cycle-dependent regulatory signaling events dissolve cohesion and promote centrosome separation in preparation for bipolar spindle assembly at mitosis. Cohesion is regulated by the antagonistic activities of the mitotic NIMA-related kinase 2 (Nek2), protein phosphatase 1, the cohesion fiber components rootletin, centrosomal Nek2-associated protein 1 (C-Nap1) and Cep68. The centrosomal protein Cep68 is essential for centrosome cohesion and dissociates from centrosomes at the onset of mitosis. Here, our cell line studies show the C-terminal 300-400 amino acids of Cep68 are necessary to localize Cep68 to interphase centrosomes while C-terminal 400-500 amino acids might regulate Cep68 dissociation from centrosomes at mitotic onset. In addition, Nek2 was demonstrated to phosphorylate Cep68 in vivo and this phosphorylation appears to promote Cep68 degradation in mitosis. We further show that the SCF complex destroys Cep68 at mitosis through recognition by the beta-Trcp F box component of SCF. Together, the findings provide a new insight into the control of centrosome separation by Cep68 during mitosis. Copyright © 2015 Elsevier GmbH. All rights reserved.
    European Journal of Cell Biology 02/2015; 426. DOI:10.1016/j.ejcb.2015.01.004 · 3.70 Impact Factor

Full-text (2 Sources)

Download
122 Downloads
Available from
Jun 3, 2014

Edgar Kramer