Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1.
Exit from mitosis requires the degradation of regulatory proteins including the mitotic cyclins and securin through ubiquitination by the anaphase promoting complex (APC) bound to Cdc20 or Cdh1. Cdc20-APC is regulated through inhibition by the spindle assembly checkpoint protein MAD2. Knowledge of Cdh1-APC regulation is limited to the phosphorylation-dependent dissociation of Cdh1 from APC. We report a novel means of regulating Cdh1 by the MAD2-related gene, MAD2L2. MAD2L2 specifically binds and inhibits Cdh1-APC, paralleling 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.
Pfleger
C M
CM
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Salic
A
A
Lee
E
E
Kirschner
M W
MW
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D005656:Fungal Proteins; D008025:Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064246:Mad2 Proteins; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014981:Xenopus
D048868:Adaptor Proteins, Signal Transducing; C577495:CDC20 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C577695:MAD2 protein, S cerevisiae; C432667:MAD2L2 protein, Xenopus; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases