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PMID: 15198982 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae.

Genes & development ·Vol. 18 ·No. 12 ·2004-06-15 ·Pages 1439-51

Pan J, Chen RH

Abstract

The spindle checkpoint arrests cells at the metaphase-to-anaphase transition until all chromosomes have properly attached to the mitotic spindle. Checkpoint proteins Mad2p and Mad3p/BubR1p bind and inhibit Cdc20p, an activator for the anaphase-promoting complex (APC). We find that upon spindle checkpoint activation by microtubule inhibitors benomyl or nocodazole, wild-type Saccharomyces cerevisiae contains less Cdc20p than spindle checkpoint mutants do, whereas their CDC20 mRNA levels are similar. The difference in Cdc20p levels correlates with their difference in the half-lives of Cdc20p, indicating that the spindle checkpoint destabilizes Cdc20p. This process requires the association between Cdc20p and Mad2p, and functional APC, but is independent of the known destruction boxes in Cdc20p and the other APC activator Cdh1p. Importantly, destabilization of Cdc20p is important for the spindle checkpoint, because a modest overexpression of Cdc20p causes benomyl sensitivity and premature Pds1p degradation in cells treated with nocodazole. Our study suggests that the spindle checkpoint reduces Cdc20p to below a certain threshold level to ensure a complete inhibition of Cdc20p before anaphase.

MeSH Terms
Anaphase Anaphase-Promoting Complex-Cyclosome Carrier Proteins/genetics,metabolism Cdc20 Proteins Cell Cycle Proteins/analysis,metabolism Down-Regulation Half-Life Mad2 Proteins Mutation Nocodazole/pharmacology Nuclear Proteins Protein Binding Saccharomyces cerevisiae Proteins/analysis,metabolism Spindle Apparatus Ubiquitin-Protein Ligase Complexes/metabolism
Chemicals
CDC20 protein, S cerevisiae Carrier Proteins Cdc20 Proteins Cell Cycle Proteins MAD2 protein, S cerevisiae Mad2 Proteins Nuclear Proteins Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Nocodazole
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pan Jing
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Chen Rey-Huei
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1184204
Published
2004-06-15
Pages
1439-51
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC423194
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1184204 PMC Full Text View journal details
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