BUB1B

Created on Dec. 19, 2012, 4:21 p.m. by Hevok & updated by Hevok on May 2, 2013, 4:55 p.m.

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 [15208629].

Bub1b/BUB1B contributes to proper chromosome segregation also by regulation of the chromosome-spindle attachments [19154723; 15592459].

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 [23242215].

References

Baker, D. J. et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat. Genet. 36, 744–749 (2004).

Lampson, M. A. & Kapoor, T. M. The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. Nat. Cell Biol. 7, 93–98 (2005).

Malureanu, L. A. et al. BubR1 N terminus acts as a soluble inhibitor of cyclin B degradation by APC/C(Cdc20) in interphase. Dev. Cell 16, 118–131 (2009).

Matsumoto, T. et al. Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke 38, 1050–1056 (2007).

Hartman, T. K., Wengenack, T. M., Poduslo, J. F. & van Deursen, J. M. Mutant mice with small amounts of BubR1 display accelerated age-related gliosis. Neurobiol. Aging 28, 921–927 (2007).

Baker, D. J. et al. Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nat. Cell Biol. 10, 825–836 (2008).

Matsuura, S. et al. Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am. J. Med. Genet. A 140, 358–367 (2006).

Hanks, S. et al. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat. Genet. 36, 1159–1161 (2004).

Burtner, C. R. & Kennedy, B. K. Progeria syndromes and ageing: what is the connection? Nat. Rev. Mol. Cell Biol. 11, 567–578 (2010).

BUBR1.jpg

Tags: aging, cancer, mitosis, gene
Categories: News
Parent: Factor

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