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Gene Review

BUB1B  -  BUB1 mitotic checkpoint serine/threonine...

Homo sapiens

Synonyms: BUB1beta, BUBR1, Bub1A, MAD3/BUB1-related protein kinase, MAD3L, ...
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Disease relevance of BUB1B


High impact information on BUB1B


Biological context of BUB1B

  • Microcell-mediated transfer of chromosome 15 (containing BUB1B) into the cells restored normal BubR1 levels, kinetochore localization of p55cdc, and the normal responses to colcemid treatment [7].
  • Monoallelic BUB1B mutations were found in all seven families studied: a single-base deletion (1833delT) in four families; and a splice site mutation, a nonsense mutation, and a missense mutation in one family each [7].
  • Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome [7].
  • Finally, hBUBR1 was associated with the cyclosome/anaphase-promoting complex (APC) in mitotically arrested cells but not in interphase cells [6].
  • Additionally, hBUBR1 is essential for normal mitotic progression as it prevents cells from prematurely entering anaphase [6].

Anatomical context of BUB1B


Associations of BUB1B with chemical compounds

  • Spindle checkpoint activation by nocodazole treatment enhances the association between p55CDC and His6-BUBR1 [8].
  • We found a glutamine/arginine polymorphism at codon 349 of the hBUBR1 gene, encoding a protein kinase required for spindle assembly checkpoint function [12].
  • A previous study by our group found nickel-titanium (NiTi) 0.02 hand files maintained the original canal shape better than similar stainless-steel K-files (SS-K) [13].

Enzymatic interactions of BUB1B

  • The results suggest that BRCA2 protein might be involved in a mitotic checkpoint in vivo after it has been phosphorylated by hBUBR1 [14].

Other interactions of BUB1B

  • This suggest that while regulation of expression of these genes may be important in cancer, the lack of putative deleterious mutations in the coding sequence does not support a frequent role for mutant hBUB1 and hBUB1B alleles in the pathogenesis of breast cancer [1].
  • BUB1 was overexpressed in 84%, BUBR1 in 68%, and BUB3 in 79% of gastric cancers [11].
  • Potential role of BRCA2 in a mitotic checkpoint after phosphorylation by hBUBR1 [14].
  • These studies have revealed mutation of the mitotic checkpoint regulators BUB1 and BUBR1 and amplification of STK15 in a subset of CIN colon cancers [15].
  • We also observed a known polymorphism at hBUBR1 codon 349 (CAA/CGA, Gln/Arg), with an allelic frequency of 0.75 for Gln and 0.25 for Arg, which is similar to that among healthy Caucasian individuals (0.73 vs 0.27) [16].

Analytical, diagnostic and therapeutic context of BUB1B


  1. Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines. Myrie, K.A., Percy, M.J., Azim, J.N., Neeley, C.K., Petty, E.M. Cancer Lett. (2000) [Pubmed]
  2. The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis. Jablonski, S.A., Chan, G.K., Cooke, C.A., Earnshaw, W.C., Yen, T.J. Chromosoma (1998) [Pubmed]
  3. Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Hanks, S., Coleman, K., Summersgill, B., Messahel, B., Williamson, D., Pritchard-Jones, K., Strefford, J., Swansbury, J., Plaja, A., Shipley, J., Rahman, N. Cancer Lett. (2006) [Pubmed]
  4. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Hanks, S., Coleman, K., Reid, S., Plaja, A., Firth, H., Fitzpatrick, D., Kidd, A., Méhes, K., Nash, R., Robin, N., Shannon, N., Tolmie, J., Swansbury, J., Irrthum, A., Douglas, J., Rahman, N. Nat. Genet. (2004) [Pubmed]
  5. Telomere-independent homologue pairing and checkpoint escape of accessory ring chromosomes in male mouse meiosis. Voet, T., Liebe, B., Labaere, C., Marynen, P., Scherthan, H. J. Cell Biol. (2003) [Pubmed]
  6. Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. Chan, G.K., Jablonski, S.A., Sudakin, V., Hittle, J.C., Yen, T.J. J. Cell Biol. (1999) [Pubmed]
  7. Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Matsuura, S., Matsumoto, Y., Morishima, K., Izumi, H., Matsumoto, H., Ito, E., Tsutsui, K., Kobayashi, J., Tauchi, H., Kajiwara, Y., Hama, S., Kurisu, K., Tahara, H., Oshimura, M., Komatsu, K., Ikeuchi, T., Kajii, T. Am. J. Med. Genet. A (2006) [Pubmed]
  8. p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase. Wu, H., Lan, Z., Li, W., Wu, S., Weinstein, J., Sakamoto, K.M., Dai, W. Oncogene (2000) [Pubmed]
  9. Identification of a novel gene--SSK1--in human endothelial cells exposed to shear stress. Donadelli, R., Benatti, L., Remuzzi, A., Morigi, M., Gullans, S.R., Benigni, A., Remuzzi, G., Noris, M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  10. Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival. Shichiri, M., Yoshinaga, K., Hisatomi, H., Sugihara, K., Hirata, Y. Cancer Res. (2002) [Pubmed]
  11. Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer--association with tumour cell proliferation. Grabsch, H., Takeno, S., Parsons, W.J., Pomjanski, N., Boecking, A., Gabbert, H.E., Mueller, W. J. Pathol. (2003) [Pubmed]
  12. A Gln/Arg polymorphism at codon 349 of the hBUBR1 gene. Katagiri, T., Futamura, M., Nakamura, Y. J. Hum. Genet. (1999) [Pubmed]
  13. Evaluation of success rate of endodontic treatment performed by students with stainless-steel K-files and nickel-titanium hand files. Pettiette, M.T., Delano, E.O., Trope, M. Journal of endodontics. (2001) [Pubmed]
  14. Potential role of BRCA2 in a mitotic checkpoint after phosphorylation by hBUBR1. Futamura, M., Arakawa, H., Matsuda, K., Katagiri, T., Saji, S., Miki, Y., Nakamura, Y. Cancer Res. (2000) [Pubmed]
  15. Genomic instability and colon cancer. Grady, W.M. Cancer Metastasis Rev. (2004) [Pubmed]
  16. Mutation analysis of hBUB1, hBUBR1 and hBUB3 genes in glioblastomas. Reis, R.M., Nakamura, M., Masuoka, J., Watanabe, T., Colella, S., Yonekawa, Y., Kleihues, P., Ohgaki, H. Acta Neuropathol. (2001) [Pubmed]
  17. BUBR1 phosphorylation is regulated during mitotic checkpoint activation. Li, W., Lan, Z., Wu, H., Wu, S., Meadows, J., Chen, J., Zhu, V., Dai, W. Cell Growth Differ. (1999) [Pubmed]
  18. Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. Sato, M., Sekido, Y., Horio, Y., Takahashi, M., Saito, H., Minna, J.D., Shimokata, K., Hasegawa, Y. Jpn. J. Cancer Res. (2000) [Pubmed]
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