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

TitleHBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint.
Publication TypeJournal Article
Year of Publication2008
JournalOncogene
Volume27
Issue24
Pagination3457-64
Date Published2008
ISSN0950-9232
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 (HBx(1-100)) 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.

URLhttp://dx.doi.org/10.1038/sj.onc.1210998
DOI10.1038/sj.onc.1210998
Short TitleOncogene
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