BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD)

Y. Niikura, H. Ogi, K. Kikuchi, K. Kitagawa

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The cell death mechanism that prevents aneuploidy caused by a failure of the spindle checkpoint has recently emerged as an important regulatory paradigm. We previously identified a new type of mitotic cell death, termed caspase-independent mitotic death (CIMD), which is induced during early mitosis by partial BUB1 (a spindle checkpoint protein) depletion and defects in kinetochore-microtubule attachment. In this study, we have shown that survived cells that escape CIMD have abnormal nuclei, and we have determined the molecular mechanism by which BUB1 depletion activates CIMD. The BUB3 protein (a BUB1 interactor and a spindle checkpoint protein) interacts with p73 (a homolog of p53), specifically in cells wherein CIMD occurs. The BUB3 protein that is freed from BUB1 associates with p73 on which Y99 is phosphorylated by c-Abl tyrosine kinase, resulting in the activation of CIMD. These results strongly support the hypothesis that CIMD is the cell death mechanism protecting cells from aneuploidy by inducing the death of cells prone to substantial chromosome missegregation.

Original languageEnglish (US)
Pages (from-to)1011-1024
Number of pages14
JournalCell Death and Differentiation
Issue number6
StatePublished - Jun 2010
Externally publishedYes


  • Aneuploidy
  • BUB3
  • C-Abl
  • P73
  • Spindle checkpoint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD)'. Together they form a unique fingerprint.

Cite this