HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint

S. Kim, S. Y. Park, H. Yong, J. K. Famulski, S. Chae, J. H. Lee, C. M. Kang, Hideyuki Saya, G. K. Chan, H. Cho

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Accurate chromosomal segregation is monitored by the mitotic checkpoint, and an increased rate of chromosomal missegregation leads to chromosomal instability (CIN). Here, we demonstrate that the HBV X protein (HBx) binds BubR1, a component of the mitotic checkpoint complex and co-localizes with BubR1 at the kinetochores. HBx binding to BubR1 attenuates the association between BubR1 and CDC20, an activator of the anaphase-promoting complex/cyclosome (APC/C) and induces slippage of mitotic arrest in the presence of microtubule poisons. In addition, HBx binding to BubR1 results in the accumulation of lagging chromosomes and chromosome bridges. In contrast, a C-terminally truncated HBx mutant (HBx1-100) fails to bind BubR1 and does not cause aberrant chromosomal segregation. This provides a novel mechanism for dysregulation of the mitotic checkpoint by a viral pathogen linking it to the accumulation of chromosomal instability in HBV-associated hepatocarcinogenesis.

Original languageEnglish
Pages (from-to)3457-3464
Number of pages8
JournalOncogene
Volume27
Issue number24
DOIs
Publication statusPublished - 2008 May 29

Fingerprint

M Phase Cell Cycle Checkpoints
Chromosomal Instability
Protein Binding
Chromosomes
Anaphase-Promoting Complex-Cyclosome
Kinetochores
Poisons
Microtubules
hepatitis B virus X protein

Keywords

  • BubR1
  • Chromosome instability
  • HBV X
  • Mitotic checkpoint

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Kim, S., Park, S. Y., Yong, H., Famulski, J. K., Chae, S., Lee, J. H., ... Cho, H. (2008). HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint. Oncogene, 27(24), 3457-3464. https://doi.org/10.1038/sj.onc.1210998

HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint. / Kim, S.; Park, S. Y.; Yong, H.; Famulski, J. K.; Chae, S.; Lee, J. H.; Kang, C. M.; Saya, Hideyuki; Chan, G. K.; Cho, H.

In: Oncogene, Vol. 27, No. 24, 29.05.2008, p. 3457-3464.

Research output: Contribution to journalArticle

Kim, S, Park, SY, Yong, H, Famulski, JK, Chae, S, Lee, JH, Kang, CM, Saya, H, Chan, GK & Cho, H 2008, 'HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint', Oncogene, vol. 27, no. 24, pp. 3457-3464. https://doi.org/10.1038/sj.onc.1210998
Kim S, Park SY, Yong H, Famulski JK, Chae S, Lee JH et al. HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint. Oncogene. 2008 May 29;27(24):3457-3464. https://doi.org/10.1038/sj.onc.1210998
Kim, S. ; Park, S. Y. ; Yong, H. ; Famulski, J. K. ; Chae, S. ; Lee, J. H. ; Kang, C. M. ; Saya, Hideyuki ; Chan, G. K. ; Cho, H. / HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint. In: Oncogene. 2008 ; Vol. 27, No. 24. pp. 3457-3464.
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