Cm. Pfleger et al., Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1, GENE DEV, 15(14), 2001, pp. 1759-1764
Exit from mitosis requires the degradation of regulatory proteins including
the mitotic cyclins and securin through ubiquitination by the anaphase pro
moting complex (APC) bound to Cdc20 or Cdh1. Cdc20-APC is regulated through
inhibition by the spindle assembly checkpoint protein MAD2. Knowledge of C
dh1-APC regulation is limited to the phosphorylation-dependent dissociation
of Cdh1 from APC. We report a novel means of regulating Cdh1 by the MAD2-r
elated gene, MAD2L2. MAD2L2 specifically binds and inhibits Cdh1-APC, paral
leling the effect of MAD2 on Cdc20. We suggest that MAD2L2 and MAD2 inhibit
the release of substrates from APC and propose a mechanism of inhibition.