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PMID: 11459825 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1.

Genes & development ·Vol. 15 ·No. 14 ·2001-07-15 ·Pages 1759-64

Pfleger CM, Salic A, Lee E, Kirschner MW

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Anaphase-Promoting Complex-Cyclosome Animals Calcium-Binding Proteins Carrier Proteins/genetics,metabolism Cdc20 Proteins Cell Cycle Proteins/metabolism Cloning, Molecular Fungal Proteins Ligases/antagonists & inhibitors,metabolism Mad2 Proteins Mitosis/physiology Molecular Sequence Data Nuclear Proteins Protein Binding Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid Ubiquitin-Protein Ligase Complexes Ubiquitin-Protein Ligases Xenopus
Chemicals
Adaptor Proteins, Signal Transducing CDC20 protein, S cerevisiae Calcium-Binding Proteins Carrier Proteins Cdc20 Proteins Cell Cycle Proteins Fungal Proteins MAD2 protein, S cerevisiae MAD2L2 protein, Xenopus Mad2 Proteins Nuclear Proteins Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Ubiquitin-Protein Ligases Ligases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pfleger C M
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Salic A
Lee E
Kirschner M W
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33 references, click to expand
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.897901
Published
2001-07-15
Pages
1759-64
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312740
Subset
IM
Grants
NIGMS NIH HHS · R01 GM026875 · United States
NIGMS NIH HHS · R01 GM039023 · United States
NIGMS NIH HHS · GM26875 · United States
NIGMS NIH HHS · GM39023 · United States
External Links
PubMed source DOI: 10.1101/gad.897901 PMC Full Text View journal details
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