The Mouse Mitotic Checkpoint Gene Bub1b, a Novel Bub1 Family Member, Is Expressed in a Cell Cycle-Dependent Manner

Abstract

A search for genes differentially expressed in normal and leukemic mouse thymocytes yielded a homolog of the yeast mitotic checkpoint protein Bub1. This novel protein (“mBub1b”) has 40% sequence similarity to the mouse Bub1 (“mBub1a”) previously described by Taylor and McKeon (1997,Cell 89,727–735) over four extended domains. 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. Northern blots of normal tissues show that mouse Bub1a and Bub1b genes are expressed in thymus and spleen, but not in nondividing tissues. In synchronized cells, expression of both Bub1 genes is undetectable in G1; Bub1 gene expression peaks in G2/M with Bub1b delayed by 6 h relative to Bub1a. This cell cycle-dependent expression explains the tissue distribution and the abundance of Bub1 mRNAs in rapidly dividing cell lines. The human equivalent of mBub1b was isolated and mapped to chromosome 15q15. The existence in mammals of two separate Bub1 genes encoding distinct proteins, coupled with the different timing of peak expression, suggests that Bub1a and Bub1b have distinct roles in the mitotic checkpoint.