The mouse mitotic checkpoint gene Bub1b, a novel Bub1 family member, is expressed in a cell cycle-dependent manner

The mouse mitotic checkpoint gene Bub1b, a novel Bub1 family member, is expressed in a cell cycle-dependent manner
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DOI:
10.1006/geno.1998.5629
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发表时间:
1999-01-01
期刊:
影响因子:
4.4
通讯作者:
Goorha, R
Goorha, R
中科院分区:
生物学3区
文献类型:
--
作者:
Davenport, JW;Fernandes, ER;Goorha, R

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在正常小鼠胸腺细胞和白血病小鼠胸腺细胞中差异表达的基因的搜索产生了酵母有丝分裂检查点蛋白Bub1的同源物。这种新蛋白(“mBub1b”)在四个扩展结构域上与Taylor和McKeon (1997, Cell 89, 727-735)先前描述的小鼠Bub1(“mBub1a”)具有40%的序列相似性。Bub1序列之间的差异表明,这两种蛋白质可能具有不同的底物特异性,并且Bub1b单独具有一个假定的“破坏”盒,可以在有丝分裂期间靶向蛋白质被蛋白酶体降解。正常组织的Northern blot显示小鼠Bub1a和Bub1b基因在胸腺和脾脏中表达,而在非分裂组织中不表达。在同步细胞中,在G中检测不到这两个Bub1基因的表达(1);Bub1基因表达在G(2)/M处达到峰值,Bub1b相对于Bub1a延迟6小时,这种细胞周期依赖性表达解释了快速分裂细胞系中Bub1 mrna的组织分布和丰度。mBub1b的人类等同物被分离并定位到染色体15q15上。哺乳动物中存在两个独立的Bub1基因,编码不同的蛋白质,加上不同的峰值表达时间,表明Bub1a和Bub1b在有丝分裂检查点中具有不同的作用。(C) 1999学术出版社。
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 G(1); Bub1 gene expression peaks in G(2)/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. (C) 1999 Academic Press.