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Gene Review

Bub1  -  budding uninhibited by benzimidazoles 1...

Mus musculus

Synonyms: AL022991, BUB1A, Bub1a, C80208, D2Xrf87, ...
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Disease relevance of Bub1

  • This report demonstrates that Bub1 and BubR1 mutant proteins from Brca2-/- thymic lymphomas have defects in the phosphorylation and kinetochore localization after spindle damage [1].
  • Whereas the exact details of this mechanism remain unclear, our novel findings raise the possibility of exploiting Bub1 as a new therapeutic target in the treatment of prostate cancer, the most common cancer in adult men in North America. (Mol Cancer Res 2006;4(12):957-69) [2].

High impact information on Bub1

  • Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage [3].
  • In Xenopus oocytes, the spindle assembly checkpoint (SAC) kinase Bub1 is required for cytostatic factor (CSF)-induced metaphase arrest in meiosis II [4].
  • Our data indicate that mAsh1 negatively regulates the cell cycle (e.g., via enhanced Cdkn2d, Bub1 expression), promotes differentiation (e.g., through effects on cAMP), and enhances survival by inhibiting apoptosis [5].
  • We report that, despite high-level expression of dominant-negative Bub1 (Bub1DN), a protein known to inhibit spindle checkpoint activity in cultured cells, thymocytes show no evidence of spindle checkpoint impairment [6].
  • Differences between the Bub1 sequences suggest that the two proteins may have different substrate specificities and that Bub1b alone has a putative "destruction" box that can target proteins for degradation by proteosomes during mitosis [7].

Chemical compound and disease context of Bub1

  • In particular, the spindle checkpoint component Bub1 was persistently up-regulated from early to advanced androgen-independent prostate cancer lesions [2].

Biological context of Bub1


Anatomical context of Bub1

  • Northern blots of normal tissues show that mouse Bub1a and Bub1b genes are expressed in thymus and spleen, but not in nondividing tissues [7].
  • In addition, we depicted the localization dynamics of Bub1 in response to spindle damage and its relationship with microtubules and chromosomes, providing further evidence for Bub1's role as a spindle checkpoint protein [8].

Associations of Bub1 with chemical compounds


Regulatory relationships of Bub1

  • In the present study we blocked the function of Bub1 during meiosis by microinjecting anti-Bub1 specific antibody into cytoplasm of mouse oocytes, and found that depletion of Bub1 induced evident cyclin B degradation and precocious anaphase onset [8].

Other interactions of Bub1

  • Thymic lymphomas from Brca2-mutant mice harbor mutations in p53, Bub1, and BubR1, which function as mitotic checkpoint proteins [1].

Analytical, diagnostic and therapeutic context of Bub1


  1. Impaired phosphorylation and mis-localization of Bub1 and BubR1 are responsible for the defective mitotic checkpoint function in Brca2-mutant thymic lymphomas. Lee, H. Exp. Mol. Med. (2003) [Pubmed]
  2. Bub1 Up-Regulation and Hyperphosphorylation Promote Malignant Transformation in SV40 Tag-Induced Transgenic Mouse Models. Guo, C., Wu, G., Chin, J.L., Bauman, G., Moussa, M., Wang, F., Greenberg, N.M., Taylor, S.S., Xuan, J.W. Mol. Cancer Res. (2006) [Pubmed]
  3. Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Taylor, S.S., McKeon, F. Cell (1997) [Pubmed]
  4. The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes. Tsurumi, C., Hoffmann, S., Geley, S., Graeser, R., Polanski, Z. J. Cell Biol. (2004) [Pubmed]
  5. RNA interference of achaete-scute homolog 1 in mouse prostate neuroendocrine cells reveals its gene targets and DNA binding sites. Hu, Y., Wang, T., Stormo, G.D., Gordon, J.I. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. A dominant interfering Bub1 mutant is insufficient to induce or alter thymic tumorigenesis in vivo, even in a sensitized genetic background. Cowley, D.O., Muse, G.W., Van Dyke, T. Mol. Cell. Biol. (2005) [Pubmed]
  7. The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner. Davenport, J.W., Fernandes, E.R., Harris, L.D., Neale, G.A., Goorha, R. Genomics (1999) [Pubmed]
  8. Bub1 prevents chromosome misalignment and precocious anaphase during mouse oocyte meiosis. Yin, S., Wang, Q., Liu, J.H., Ai, J.S., Liang, C.G., Hou, Y., Chen, D.Y., Schatten, H., Sun, Q.Y. Cell Cycle (2006) [Pubmed]
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