BUB1B

This gene encodes a kinase involved in spindle checkpoint function and chromosome segregation.{{cite journal | vauthors = Guo Y, Kim C, Ahmad S, Zhang J, Mao Y | title = CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint | journal = The Journal of Cell Biology | volume = 198 | issue = 2 | pages = 205–217 | date = July 2012 | pmid = 22801780 | pmc = 3410423 | doi = 10.1083/jcb.201202152 }} The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer.{{cite web | title = Entrez Gene: BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=701}}

Increased expression of BubR1 in mice extends a healthy lifespan.{{cite journal | vauthors = Baker DJ, Dawlaty MM, Wijshake T, Jeganathan KB, Malureanu L, van Ree JH, Crespo-Diaz R, Reyes S, Seaburg L, Shapiro V, Behfar A, Terzic A, van de Sluis B, van Deursen JM | display-authors = 6 | title = Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan | journal = Nature Cell Biology | volume = 15 | issue = 1 | pages = 96–102 | date = January 2013 | pmid = 23242215 | pmc = 3707109 | doi = 10.1038/ncb2643 }}

• {{cite web |date=December 17, 2012 |title=Mayo Clinic Study Unmasks Regulator of Healthy Life Span |website=Mayo Clinic |url=http://www.mayoclinic.org/news2012-rst/7212.html}}

BubR1 has been implicated in a variety of biological processes and pathologies, including cancer, aging, mosaic variegated aneuploidy (MVA), and heart disease. BubR1 protein levels are shown to decline with age.{{cite journal | vauthors = Baker DJ, Jeganathan KB, Cameron JD, Thompson M, Juneja S, Kopecka A, Kumar R, Jenkins RB, de Groen PC, Roche P, van Deursen JM | display-authors = 6 | title = BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice | journal = Nature Genetics | volume = 36 | issue = 7 | pages = 744–749 | date = July 2004 | pmid = 15208629 | doi = 10.1038/ng1382 | s2cid = 7871496 | doi-access = free }}{{cite journal | vauthors = Bloom CR, North BJ | title = Physiological relevance of post-translational regulation of the spindle assembly checkpoint protein BubR1 | journal = Cell & Bioscience | volume = 11 | issue = 1 | pages = 76 | date = April 2021 | pmid = 33892776 | pmc = 8066494 | doi = 10.1186/s13578-021-00589-2 | doi-access = free }} Furthermore, loss of BubR1 in young organisms is associated with rapid aging and premature onset of age-related diseases and phenotypes such as cardiac dysfunction, poor wound healing, cataracts, kyphosis, fat loss and muscle wasting (cachexia), and cancer. This has been demonstrated in mice.

Chemoradiotherapy (CRT), the combination of chemotherapy and radiotherapy applied with curative intent, is used to treat a variety of cancers. CRT acts by inducing damage in the DNA of the cancer cells. Bladder cancer tumor samples were taken from patients before treatment and from the same patients after CRT treatment when the tumors had reoccurred.{{cite journal | vauthors = Komura K, Inamoto T, Tsujino T, Matsui Y, Konuma T, Nishimura K, Uchimoto T, Tsutsumi T, Matsunaga T, Maenosono R, Yoshikawa Y, Taniguchi K, Tanaka T, Uehara H, Hirata K, Hirano H, Nomi H, Hirose Y, Ono F, Azuma H | display-authors = 6 | title = Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents | journal = Oncogene | volume = 40 | issue = 43 | pages = 6210–6222 | date = October 2021 | pmid = 34545188 | pmc = 8553621 | doi = 10.1038/s41388-021-02021-y }} An increased level of BUB1B expression was found in the CRT-recurrent cells. This increased expression was considered to facilitate an inaccurate DNA repair process termed alternative non-homologous end joining (A-NHEJ) that inaccurately repairs DNA damages such as those caused by the CRT. This inaccurate repair could cause additional mutations in the tumor including mutations to CRT resistance.

BUB1B has been shown to interact with:

• AP2B1{{cite journal | vauthors = Cayrol C, Cougoule C, Wright M | title = The beta2-adaptin clathrin adaptor interacts with the mitotic checkpoint kinase BubR1 | journal = Biochemical and Biophysical Research Communications | volume = 298 | issue = 5 | pages = 720–730 | date = November 2002 | pmid = 12419313 | doi = 10.1016/S0006-291X(02)02522-6 }}
• BRCA2{{cite journal | vauthors = Futamura M, Arakawa H, Matsuda K, Katagiri T, Saji S, Miki Y, Nakamura Y | title = Potential role of BRCA2 in a mitotic checkpoint after phosphorylation by hBUBR1 | journal = Cancer Research | volume = 60 | issue = 6 | pages = 1531–1535 | date = March 2000 | pmid = 10749118 }}
• BUB3{{cite journal | vauthors = Hoyt MA | title = A new view of the spindle checkpoint | journal = The Journal of Cell Biology | volume = 154 | issue = 5 | pages = 909–911 | date = September 2001 | pmid = 11535614 | pmc = 2196198 | doi = 10.1083/jcb.200108010 }}{{cite journal | vauthors = Taylor SS, Ha E, McKeon F | title = The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase | journal = The Journal of Cell Biology | volume = 142 | issue = 1 | pages = 1–11 | date = July 1998 | pmid = 9660858 | pmc = 2133037 | doi = 10.1083/jcb.142.1.1 }}
• CDC20{{cite journal | vauthors = Fang G | title = Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex | journal = Molecular Biology of the Cell | volume = 13 | issue = 3 | pages = 755–766 | date = March 2002 | pmid = 11907259 | pmc = 99596 | doi = 10.1091/mbc.01-09-0437 }}{{cite journal | vauthors = Wu H, Lan Z, Li W, Wu S, Weinstein J, Sakamoto KM, Dai W | title = p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase | journal = Oncogene | volume = 19 | issue = 40 | pages = 4557–4562 | date = September 2000 | pmid = 11030144 | doi = 10.1038/sj.onc.1203803 | s2cid = 23544995 | doi-access = }}{{cite journal | vauthors = Kallio MJ, Beardmore VA, Weinstein J, Gorbsky GJ | title = Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes in mammalian cells | journal = The Journal of Cell Biology | volume = 158 | issue = 5 | pages = 841–847 | date = September 2002 | pmid = 12196507 | pmc = 2173153 | doi = 10.1083/jcb.200201135 }}{{cite journal | vauthors = Skoufias DA, Andreassen PR, Lacroix FB, Wilson L, Margolis RL | title = Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 8 | pages = 4492–4497 | date = April 2001 | pmid = 11274370 | pmc = 31862 | doi = 10.1073/pnas.081076898 | doi-access = free | bibcode = 2001PNAS...98.4492S }}{{cite journal | vauthors = Nilsson J, Yekezare M, Minshull J, Pines J | title = The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction | journal = Nature Cell Biology | volume = 10 | issue = 12 | pages = 1411–1420 | date = December 2008 | pmid = 18997788 | pmc = 2635557 | doi = 10.1038/ncb1799 }}
• MAD2L1{{cite journal | vauthors = Sudakin V, Chan GK, Yen TJ | title = Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 | journal = The Journal of Cell Biology | volume = 154 | issue = 5 | pages = 925–936 | date = September 2001 | pmid = 11535616 | pmc = 2196190 | doi = 10.1083/jcb.200102093 }}
• CBP{{cite journal | vauthors = North BJ, Rosenberg MA, Jeganathan KB, Hafner AV, Michan S, Dai J, Baker DJ, Cen Y, Wu LE, Sauve AA, van Deursen JM, Rosenzweig A, Sinclair DA | display-authors = 6 | title = SIRT2 induces the checkpoint kinase BubR1 to increase lifespan | journal = The EMBO Journal | volume = 33 | issue = 13 | pages = 1438–1453 | date = July 2014 | pmid = 24825348 | pmc = 4194088 | doi = 10.15252/embj.201386907 }}
• SIRT2{{cite journal | vauthors = Suematsu T, Li Y, Kojima H, Nakajima K, Oshimura M, Inoue T | title = Deacetylation of the mitotic checkpoint protein BubR1 at lysine 250 by SIRT2 and subsequent effects on BubR1 degradation during the prometaphase/anaphase transition | journal = Biochemical and Biophysical Research Communications | volume = 453 | issue = 3 | pages = 588–594 | date = October 2014 | pmid = 25285631 | doi = 10.1016/j.bbrc.2014.09.128 }}{{cite journal | vauthors = Qiu D, Hou X, Han L, Li X, Ge J, Wang Q | title = Sirt2-BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality | journal = Aging Cell | volume = 17 | issue = 1 | pages = e12698 | date = February 2018 | pmid = 29067790 | doi = 10.1111/acel.12698 | pmc = 5770883 }}
• PLK1{{cite journal | vauthors = Huang H, Hittle J, Zappacosta F, Annan RS, Hershko A, Yen TJ | title = Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit | journal = The Journal of Cell Biology | volume = 183 | issue = 4 | pages = 667–680 | date = November 2008 | pmid = 19015317 | pmc = 2582891 | doi = 10.1083/jcb.200805163 }}{{cite journal | vauthors = Matsumura S, Toyoshima F, Nishida E | title = Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1 | language = English | journal = The Journal of Biological Chemistry | volume = 282 | issue = 20 | pages = 15217–15227 | date = May 2007 | pmid = 17376779 | doi = 10.1074/jbc.M611053200 | doi-access = free }}{{cite journal | vauthors = Elowe S, Hümmer S, Uldschmid A, Li X, Nigg EA | title = Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions | journal = Genes & Development | volume = 21 | issue = 17 | pages = 2205–2219 | date = September 2007 | pmid = 17785528 | doi = 10.1101/gad.436007 | pmc = 1950859 }}{{cite journal | vauthors = Izumi H, Matsumoto Y, Ikeuchi T, Saya H, Kajii T, Matsuura S | title = BubR1 localizes to centrosomes and suppresses centrosome amplification via regulating Plk1 activity in interphase cells | journal = Oncogene | volume = 28 | issue = 31 | pages = 2806–2820 | date = August 2009 | pmid = 19503101 | doi = 10.1038/onc.2009.141 | s2cid = 23514072 }}{{cite journal | vauthors = Suijkerbuijk SJ, Vleugel M, Teixeira A, Kops GJ | title = Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments | language = English | journal = Developmental Cell | volume = 23 | issue = 4 | pages = 745–755 | date = October 2012 | pmid = 23079597 | doi = 10.1016/j.devcel.2012.09.005 | doi-access = free }}
• PP2A-B56{{cite journal | vauthors = Kruse T, Zhang G, Larsen MS, Lischetti T, Streicher W, Kragh Nielsen T, Bjørn SP, Nilsson J | display-authors = 6 | title = Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression | journal = Journal of Cell Science | volume = 126 | issue = Pt 5 | pages = 1086–1092 | date = March 2013 | pmid = 23345399 | doi = 10.1242/jcs.122481 | s2cid = 30718574 | doi-access = free }}{{cite journal | vauthors = Gama Braga L, Cisneros AF, Mathieu MM, Clerc M, Garcia P, Lottin B, Garand C, Thebault P, Landry CR, Elowe S | display-authors = 6 | title = BUBR1 Pseudokinase Domain Promotes Kinetochore PP2A-B56 Recruitment, Spindle Checkpoint Silencing, and Chromosome Alignment | language = English | journal = Cell Reports | volume = 33 | issue = 7 | pages = 108397 | date = November 2020 | pmid = 33207204 | doi = 10.1016/j.celrep.2020.108397 | s2cid = 227066402 | doi-access = free }}{{cite journal | vauthors = Wang J, Wang Z, Yu T, Yang H, Virshup DM, Kops GJ, Lee SH, Zhou W, Li X, Xu W, Rao Z | display-authors = 6 | title = Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization | journal = Protein & Cell | volume = 7 | issue = 7 | pages = 516–526 | date = July 2016 | pmid = 27350047 | pmc = 4930772 | doi = 10.1007/s13238-016-0283-4 }}
• HDAC1{{cite journal | vauthors = Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang SG, Chun JS, Lee CW | display-authors = 6 | title = WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase | journal = FEBS Letters | volume = 575 | issue = 1–3 | pages = 23–29 | date = September 2004 | pmid = 15388328 | doi = 10.1016/j.febslet.2004.07.089 | s2cid = 21762011 | doi-access = free }}
• HDAC2 / HDAC3{{cite journal | vauthors = Park I, Kwon MS, Paik S, Kim H, Lee HO, Choi E, Lee H | title = HDAC2/3 binding and deacetylation of BubR1 initiates spindle assembly checkpoint silencing | journal = The FEBS Journal | volume = 284 | issue = 23 | pages = 4035–4050 | date = December 2017 | pmid = 28985013 | doi = 10.1111/febs.14286 | s2cid = 4164003 | doi-access = free }}
• SNCG{{cite journal | vauthors = Gupta A, Inaba S, Wong OK, Fang G, Liu J | title = Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1 | journal = Oncogene | volume = 22 | issue = 48 | pages = 7593–7599 | date = October 2003 | pmid = 14576821 | doi = 10.1038/sj.onc.1206880 | s2cid = 5689831 | doi-access = }}

{{reflist}}

{{refbegin | 2}}

• {{cite journal | vauthors = Posas F, Saito H | title = Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator | journal = The EMBO Journal | volume = 17 | issue = 5 | pages = 1385–1394 | date = March 1998 | pmid = 9482735 | pmc = 1170486 | doi = 10.1093/emboj/17.5.1385 }}
• {{cite journal | vauthors = Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B | display-authors = 6 | title = Mutations of mitotic checkpoint genes in human cancers | journal = Nature | volume = 392 | issue = 6673 | pages = 300–303 | date = March 1998 | pmid = 9521327 | doi = 10.1038/32688 | s2cid = 4416376 | bibcode = 1998Natur.392..300C }}
• {{cite journal | vauthors = Donadelli R, Benatti L, Remuzzi A, Morigi M, Gullans SR, Benigni A, Remuzzi G, Noris M | display-authors = 6 | title = Identification of a novel gene--SSK1--in human endothelial cells exposed to shear stress | journal = Biochemical and Biophysical Research Communications | volume = 246 | issue = 3 | pages = 881–887 | date = May 1998 | pmid = 9618306 | doi = 10.1006/bbrc.1998.8713 }}
• {{cite journal | vauthors = Chan GK, Schaar BT, Yen TJ | title = Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1 | journal = The Journal of Cell Biology | volume = 143 | issue = 1 | pages = 49–63 | date = October 1998 | pmid = 9763420 | pmc = 2132809 | doi = 10.1083/jcb.143.1.49 }}
• {{cite journal | vauthors = Jablonski SA, Chan GK, Cooke CA, Earnshaw WC, Yen TJ | title = The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis | journal = Chromosoma | volume = 107 | issue = 6–7 | pages = 386–396 | date = December 1998 | pmid = 9914370 | doi = 10.1007/s004120050322 | s2cid = 13928165 }}
• {{cite journal | vauthors = Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C | title = Characterization of MAD2B and other mitotic spindle checkpoint genes | journal = Genomics | volume = 58 | issue = 2 | pages = 181–187 | date = June 1999 | pmid = 10366450 | doi = 10.1006/geno.1999.5831 | doi-access = free }}
• {{cite journal | vauthors = Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ | title = Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC | journal = The Journal of Cell Biology | volume = 146 | issue = 5 | pages = 941–954 | date = September 1999 | pmid = 10477750 | pmc = 2169490 | doi = 10.1083/jcb.146.5.941 }}
• {{cite journal | vauthors = Li W, Lan Z, Wu H, Wu S, Meadows J, Chen J, Zhu V, Dai W | display-authors = 6 | title = BUBR1 phosphorylation is regulated during mitotic checkpoint activation | journal = Cell Growth & Differentiation | volume = 10 | issue = 11 | pages = 769–775 | date = November 1999 | pmid = 10593653 }}
• {{cite journal | vauthors = Saffery R, Irvine DV, Griffiths B, Kalitsis P, Choo KH | title = Components of the human spindle checkpoint control mechanism localize specifically to the active centromere on dicentric chromosomes | journal = Human Genetics | volume = 107 | issue = 4 | pages = 376–384 | date = October 2000 | pmid = 11129339 | doi = 10.1007/s004390000386 | s2cid = 38578162 }}
• {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–292 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}
• {{cite journal | vauthors = Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Näthke IS | title = A role for the Adenomatous Polyposis Coli protein in chromosome segregation | journal = Nature Cell Biology | volume = 3 | issue = 4 | pages = 429–432 | date = April 2001 | pmid = 11283619 | doi = 10.1038/35070123 | s2cid = 12645435 }}
• {{cite journal | vauthors = Tang Z, Bharadwaj R, Li B, Yu H | title = Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1 | journal = Developmental Cell | volume = 1 | issue = 2 | pages = 227–237 | date = August 2001 | pmid = 11702782 | doi = 10.1016/S1534-5807(01)00019-3 | doi-access = free }}
• {{cite journal | vauthors = Shichiri M, Yoshinaga K, Hisatomi H, Sugihara K, Hirata Y | title = Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival | journal = Cancer Research | volume = 62 | issue = 1 | pages = 13–17 | date = January 2002 | pmid = 11782350 }}
• {{cite journal | vauthors = Taylor SS, Hussein D, Wang Y, Elderkin S, Morrow CJ | title = Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells | journal = Journal of Cell Science | volume = 114 | issue = Pt 24 | pages = 4385–4395 | date = December 2001 | pmid = 11792804 | doi = 10.1242/jcs.114.24.4385 }}

{{refend}}

• {{UCSC gene info|BUB1B}}

{{DEFAULTSORT:Bub1b}}