Mad2-Independent Inhibition of APCCdc20 by the Mitotic Checkpoint Protein BubR1

Zhanyun Tang, Rajnish Bharadwaj, Bing Li, Hongtao Yu

Research output: Contribution to journalArticle

337 Scopus citations

Abstract

The mitotic checkpoint blocks the activation of the anaphase-promoting complex (APC) until all sister chromatids have achieved bipolar attachment to the spindle. A checkpoint complex containing BubR1 and Bub3 has been purified from mitotic human cells. Upon checkpoint activation, the BubR1 -Bub3 complex interacts with Cdc20. In the absence of Mad2, BubR1 inhibits the activity of APC by blocking the binding of Cdc20 to APC. Surprisingly, the kinase activity of BubR1 is not required for the inhibition of APCCdc20. BubR1 also prevents the activation of APCCdc20 in Xenopus egg extracts, and restores the mitotic arrest in Cdc20-overexpressing cells treated with nocodazole. Because BubR1 also interacts with the mitotic motor CENP-E, the ability of BubR1 to inhibit APC may be regulated by kinetochore tension or occupancy.

Original languageEnglish (US)
Pages (from-to)227-237
Number of pages11
JournalDevelopmental cell
Volume1
Issue number2
DOIs
StatePublished - Aug 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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