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Gene Review

BUB3  -  Bub3p

Saccharomyces cerevisiae S288c

Synonyms: Cell cycle arrest protein BUB3, OR26.16, YOR026W
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Disease relevance of BUB3


High impact information on BUB3

  • Bub3 null embryos appear normal up to day 3.5 pc but accumulate mitotic errors from days 4.5-6.5 pc in the form of micronuclei, chromatin bridging, lagging chromosomes, and irregular nuclear morphology [2].
  • Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis [2].
  • When the spindle checkpoint is activated at unattached kinetochores, the checkpoint proteins BubR1, Bub3 and Mad2 bind and inhibit Cdc20, an activator of the anaphase-promoting complex (APC) [3].
  • Moreover, during mitosis, APC localizes to the ends of microtubules embedded in kinetochores and forms a complex with the checkpoint proteins Bub1 and Bub3 [4].
  • Components of the spindle checkpoint include the mitotic arrest defective (MAD) genes MAD1-3, and the budding uninhibited by benzimidazole (BUB) genes BUB1 and BUB3 [5].

Biological context of BUB3

  • BUB3 is a checkpoint gene that permits entry into mitosis depending upon the assembly state of microtubules [6].
  • Transformation of mutant cells with genomic libraries repeatedly identified three different suppressors: the two wild-type alpha-tubulin genes, TUB1 and TUB3; and BUB3 [6].
  • A 156-amino acid fragment of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid assay [7].
  • Retention of the BUB3 checkpoint protein on lagging chromosomes [8].
  • Our findings demonstrate that GLEBS motifs reside in mammalian nucleoporins and mitotic checkpoint proteins and apparently serve as specific binding sites for either BUB3, RAE1, or both [9].

Anatomical context of BUB3

  • Excess BUB3 rescues both the loss of viability and microtubule defects but not the benomyl supersensitivity associated with tub1-729 [6].
  • The nocodazole-activated spindle checkpoint of HeLa cells was disrupted by expression of a 39 amino acid fragment (residues 382-420) of BubR1 containing the Bub3-binding GLEBS motif [10].

Associations of BUB3 with chemical compounds

  • Intriguingly, the number of lagging chromosomes with high Bub3 staining increases dramatically in cells treated with low (and pharmacologically relevant) concentrations of the chemotherapeutic taxol and the microtubule poison nocodazole [8].

Physical interactions of BUB3

  • Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage [7].

Enzymatic interactions of BUB3


Regulatory relationships of BUB3

  • A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644 [12].

Other interactions of BUB3

  • Two of the identified genes, BUB2 and BUB3, have been cloned and described (M. A. Hoyt, L. Totis, and B. T. Roberts, Cell 66:507-517, 1991) [11].
  • Mutation of this motif abolishes checkpoint function, indicating that formation of the Mad1p-Bub1p-Bub3p complex is a crucial step in the spindle checkpoint mechanism [13].
  • Comparison of the Bub3 sequence to the WD40 protein, Rae1, shows high sequence conservation along the same surfaces [14].
  • Mad3 forms a stable heterodimer with Bub3 [15].

Analytical, diagnostic and therapeutic context of BUB3


  1. Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers. Haruki, N., Saito, H., Harano, T., Nomoto, S., Takahashi, T., Osada, H., Fujii, Y., Takahashi, T. Cancer Lett. (2001) [Pubmed]
  2. Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis. Kalitsis, P., Earle, E., Fowler, K.J., Choo, K.H. Genes Dev. (2000) [Pubmed]
  3. Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpoint. Chung, E., Chen, R.H. Nat. Cell Biol. (2003) [Pubmed]
  4. A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Kaplan, K.B., Burds, A.A., Swedlow, J.R., Bekir, S.S., Sorger, P.K., Näthke, I.S. Nat. Cell Biol. (2001) [Pubmed]
  5. Spindle checkpoint proteins and chromosome-microtubule attachment in budding yeast. Gillett, E.S., Espelin, C.W., Sorger, P.K. J. Cell Biol. (2004) [Pubmed]
  6. Suppression of a conditional mutation in alpha-tubulin by overexpression of two checkpoint genes. Guénette, S., Magendantz, M., Solomon, F. J. Cell. Sci. (1995) [Pubmed]
  7. Distinct chromosome segregation roles for spindle checkpoint proteins. Warren, C.D., Brady, D.M., Johnston, R.C., Hanna, J.S., Hardwick, K.G., Spencer, F.A. Mol. Biol. Cell (2002) [Pubmed]
  8. Retention of the BUB3 checkpoint protein on lagging chromosomes. Martinez-Exposito, M.J., Kaplan, K.B., Copeland, J., Sorger, P.K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. The mitotic checkpoint protein hBUB3 and the mRNA export factor hRAE1 interact with GLE2p-binding sequence (GLEBS)-containing proteins. Wang, X., Babu, J.R., Harden, J.M., Jablonski, S.A., Gazi, M.H., Lingle, W.L., de Groen, P.C., Yen, T.J., van Deursen, J.M. J. Biol. Chem. (2001) [Pubmed]
  10. The mitotic checkpoint gene BubR1 has two distinct functions in mitosis. Harris, L., Davenport, J., Neale, G., Goorha, R. Exp. Cell Res. (2005) [Pubmed]
  11. The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Roberts, B.T., Farr, K.A., Hoyt, M.A. Mol. Cell. Biol. (1994) [Pubmed]
  12. The anti-malarial artesunate is also active against cancer. Efferth, T., Dunstan, H., Sauerbrey, A., Miyachi, H., Chitambar, C.R. Int. J. Oncol. (2001) [Pubmed]
  13. Complex formation between Mad1p, Bub1p and Bub3p is crucial for spindle checkpoint function. Brady, D.M., Hardwick, K.G. Curr. Biol. (2000) [Pubmed]
  14. Crystal structure of the spindle assembly checkpoint protein Bub3. Larsen, N.A., Harrison, S.C. J. Mol. Biol. (2004) [Pubmed]
  15. Structural analysis of Bub3 interactions in the mitotic spindle checkpoint. Larsen, N.A., Al-Bassam, J., Wei, R.R., Harrison, S.C. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  16. The 1.1-angstrom structure of the spindle checkpoint protein Bub3p reveals functional regions. Wilson, D.K., Cerna, D., Chew, E. J. Biol. Chem. (2005) [Pubmed]
  17. Molecular cloning and characterization of the human budding uninhibited by benomyl (BUB3) promoter. Baek, W.K., Park, J.W., Lim, J.H., Suh, S.I., Suh, M.H., Gabrielson, E., Kwon, T.K. Gene (2002) [Pubmed]
  18. Assignment of BUB3 to human chromosome band 10q26 by in situ hybridization. Kwon, T.K., Hawkins, A.L., Griffin, C.A., Gabrielson, E. Cytogenet. Cell Genet. (2000) [Pubmed]
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