Zhao N, Lai F, Fernald A A, Eisenbart J D, Espinosa R, Wang P W, Le Beau M M
Department of Medicine, University of Chicago, Chicago, Illinois, 60637, USA.
Genomics. 1998 Oct 15;53(2):184-90. doi: 10.1006/geno.1998.5473.
The transition from metaphase to anaphase and exit from mitosis involve the degradation of active cyclin B-CDC2 complexes by ubiquitin-mediated proteolysis. The anaphase-promoting complex (APC) catalyzes the formation of cyclin B-ubiquitin conjugates, thereby targeting cyclin B for degradation. The APC is composed of eight proteins, including four members of a family characterized by multiple tetratricopeptide repeats (TPR). We mapped two overlapping expressed sequence tag clones within a genomic contig on human chromosome 5, band q31. A search revealed high homology to Saccharomyces cerevisiae CDC23, a TPR protein component of the APC. We have isolated the human CDC23 cDNA containing the full-length predicted open reading frame. The approximately 3.3-kb message is ubiquitously expressed and encodes a protein with 591 amino acids (MW = 68,293 Da) and 9 TPR units. The protein has 30% identity and 51% similarity to the S. cerevisiae protein. The human CDC23 gene contains 16 exons and spans approximately 31 kb. CDC23 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no mutations of CDC23 in leukemia cells with loss of 5q. Thus, CDC23 is unlikely to be involved in the pathogenesis of myeloid leukemias characterized by abnormalities of chromosome 5.
从中期到后期的转变以及有丝分裂的退出涉及泛素介导的蛋白水解作用对活性细胞周期蛋白B-CDC2复合物的降解。后期促进复合物（APC）催化细胞周期蛋白B-泛素缀合物的形成，从而将细胞周期蛋白B作为降解目标。APC由八种蛋白质组成，包括一个以多个四肽重复序列（TPR）为特征的家族的四个成员。我们在人类5号染色体q31带的一个基因组重叠群中定位了两个重叠的表达序列标签克隆。搜索发现其与酿酒酵母CDC23高度同源，CDC23是APC的一种TPR蛋白成分。我们分离出了包含全长预测开放阅读框的人类CDC23 cDNA。约3.3kb的信使RNA在全身广泛表达，编码一个含有591个氨基酸（分子量 = 68,293道尔顿）和9个TPR单元的蛋白质。该蛋白质与酿酒酵母的蛋白质有30%的同一性和51%的相似性。人类CDC23基因包含16个外显子，跨度约为31kb。CDC23定位于以5号染色体缺失为特征的髓系白血病中最小的常见缺失区段内；然而，我们在5号染色体缺失的白血病细胞中未检测到CDC23的突变。因此，CDC23不太可能参与以5号染色体异常为特征的髓系白血病的发病机制。
