BUB1B (alias BubR1) is a mitotic regulator that ensures accurate segregation of chromosomes through has a role in mitotic checkpoint and the establishment of proper microtubule-kinetochore attachments.
During mitosis, duplicated chromosomes have to be separated equally amongst two identical cells. To guarantee that this process occurs without errors, mammalian cells have evolved a surveillance mechanism, the mitotic checkpoint, that inhibits anaphase onset until chromosome bi-orientation has been achieved. Bub1b is a core mitotic component that binds to and inhibits the Cdc20-activated anaphase-promoting complex, APC/C(Cdc20), a ubiquitin E3 ligase that initiates anaphase by orchestrating separase-mediated cleavage of cohesion rings that hold sister chromatids together .
Germline mutations that reduce BUB1B abundance causes aneuploidy, shorten lifespan and induce premature aging phenotypes and cancer in both mice and human [23242215; 15208629; 17272762; 16781018; 16411201; 15475955; 20651707].
Enhanced expression of Bub1b counteracts cancer and extends lifespan .
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