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MAD2B is an Inhibitor of the Anaphase-promoting Complex

Overview
Journal Genes Dev
Specialty Molecular Biology
Date 2001 Jul 19
PMID 11459826
Citations 71
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Abstract

Anaphase-promoting complex (APC), a ubiquitin ligase, controls both sister chromatid separation and mitotic exit. The APC is activated in mitosis and G1 by CDC20 and CDH1, and inhibited by the checkpoint protein MAD2, a specific inhibitor of CDC20. We show here that a MAD2 homolog MAD2B also inhibits APC. In contrast to MAD2, MAD2B inhibits both CDH1-APC and CDC20-APC. This inhibition is targeted to CDH1 and CDC20, but not directly to APC. Unlike MAD2, whose interaction with MAD1 is required for mitotic checkpoint control, MAD2B does not interact with MAD1, suggesting that MAD2B may relay a different cellular signal to APC.

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References
1.
Fang G, Yu H, Kirschner M . Control of mitotic transitions by the anaphase-promoting complex. Philos Trans R Soc Lond B Biol Sci. 1999; 354(1389):1583-90. PMC: 1692672. DOI: 10.1098/rstb.1999.0502. View

2.
Gieffers C, PETERS B, Kramer E, Dotti C, Peters J . Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. Proc Natl Acad Sci U S A. 1999; 96(20):11317-22. PMC: 18031. DOI: 10.1073/pnas.96.20.11317. View

3.
Pfleger C, Kirschner M . The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes Dev. 2000; 14(6):655-65. PMC: 316466. View

4.
Wang Y, Hu F, Elledge S . The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit. Curr Biol. 2000; 10(21):1379-82. DOI: 10.1016/s0960-9822(00)00779-x. View

5.
Pfleger C, Salic A, Lee E, Kirschner M . Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1. Genes Dev. 2001; 15(14):1759-64. PMC: 312740. DOI: 10.1101/gad.897901. View