Mitotic checkpoint protein BUB3 (BUB3)

Mitotic checkpoint protein BUB3 (BUB3) is a conserved WD40-repeat spindle assembly checkpoint protein essential for regulating the metaphase-to-anaphase transition during mitosis and meiosis. BUB3 forms core complexes with other checkpoint proteins (notably Bub1 and BubR1/Mad3) at kinetochores, ensuring correct attachment and alignment of chromosomes before cell division proceeds. By inhibiting the Anaphase Promoting Complex/Cyclosome (APC/C), BUB3 delays entry into anaphase until all chromosomes are properly oriented, which preserves chromosomal fidelity. BUB3’s function is critical for suppressing aneuploidy; thus, defective BUB3 expression or function is implicated in many cancers and other diseases associated with chromosomal instability. Structural studies show BUB3 is a seven-bladed beta-propeller protein, with conserved WD40 motifs enabling binding to partner proteins. There are no approved drugs that directly target BUB3, but disruption of its complexes is being explored for anticancer therapy given its role in checkpoint integrity. Safety concerns are significant, as spindle checkpoint inhibition carries a risk of cytotoxicity and chromosomal instability in non-tumor cells.

Other names

BUB3LhBUB3BUB3 budding uninhibited by benzimidazoles 3 homologBudding uninhibited by benomylMitotic checkpoint componentTesticular tissue protein Li 27

Agents that inhibit or disrupt BUB3 or its interaction with BubR1/Mad3 would abrogate the spindle assembly checkpoint, resulting in mitotic errors and cell death—under investigation as a possible cancer therapeutic strategy. Experimental inhibition of BUB3 induces apoptosis and inhibits cancer cell proliferation.