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The Mouse Mitotic Checkpoint Gene Bub1b,a Novel Bub1 Family Member,Is Expressed in a Cell Cycle-Dependent Manner
Institution:1. Department of Virology and Molecular Biology, St. Jude Children''s Research Hospital, Memphis, Tennessee, 38105;2. Department of Pathology, University of Tennessee, Memphis, Tennessee, 38163;1. Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China;2. Avian Disease Research Center, College of Veterinary Medicine of Sichuan Agricultural University, Ya’an, Sichuan 625014, PR China;3. Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China;1. Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan;2. Rogel Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan;3. Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan;4. Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan;5. Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan;1. Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA, USA;2. Inflamed, Inc., Louisville, KY, USA;3. The John Curtin School of Medical Research, Canberra, ACT, Australia;4. Medical School, The Australian National University, Canberra, ACT, Australia;1. Department of Central Laboratory, Shanghai Tenth People''s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China;2. School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Zhejiang, China;3. Department of Plant Science, BioSNTR, South Dakota State University, Brookings, South Dakota, USA
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.
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