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, H. Saya, G. K. Chan, H. Cho

Research output: Contribution to journalArticle

58 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 - 29-05-2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint'. Together they form a unique fingerprint.

  • Cite this

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