Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae

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Bibliographische Detailangaben
Zeitschriftentitel:	Genes & Development
Personen und Körperschaften:	Pan, Jing, Chen, Rey-Huei
In:	Genes & Development, 18, 2004, 12, S. 1439-1451
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	Cold Spring Harbor Laboratory
Schlagwörter:	Developmental Biology Genetics

Details
Zusammenfassung:	<jats:p>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 <jats:italic>Saccharomyces cerevisiae</jats:italic> contains less Cdc20p than spindle checkpoint mutants do, whereas their <jats:italic>CDC20</jats:italic> 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.</jats:p>
Umfang:	1439-1451
ISSN:	0890-9369 1549-5477
DOI:	10.1101/gad.1184204