Li H, Lahti J M, Kidd V J
Department of Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Oncogene. 1996 Aug 15;13(4):705-12.
The cyclin C protein has recently been shown to associate with a unique cyclin dependent protein kinase (cdk8) and it has been proposed that this complex may regulate RNA transcription during the cell cycle. In addition, the human cyclin C gene has been localized to human chromosome 6q21 and it was found to be frequently deleted in a subset of acute lymphoblastic leukemias (ALL's). Screening of an avian T-cell cDNA library resulted in the isolation of a cyclin C homologue as well as an abundant, yet distinct, cyclin C-related cDNA. The predicted open reading frame (ORF) of the cyclin C cDNA predicted a 283 amino acid protein that was > 99% identical to the human protein and 72% identical to the Drosophila melanogaster protein. However, the predicted ORF of the cyclin C-related cDNA predicted a much smaller 105 amino acid protein that was identical to cyclin C well into the cyclin-box region (amino acid residue 98), where it abruptly diverges and then terminates. Using PCR analysis of cDNA derived from a range of cell lines and tissues, alternative splicing of the avian cyclin C gene has been demonstrated. Furthermore, a smaller approximately 19 kDa protein that co-migrates with the in vitro transcribed and translated truncated cyclin C protein was detected in normal and virally-transformed avian cells with a cyclin C-specific antibody. Expression of alternatively spliced cyclin C mRNA and protein is regulated in a cell cycle-dependent manner reminiscent of cyclin B2. The function of this truncated cyclin C protein is not known, but its expression in avian cells suggest that this truncated cyclin C protein may participate as an early endogenously encoded cyclin C inhibitor.
细胞周期蛋白C(Cyclin C)最近被证明与一种独特的细胞周期蛋白依赖性蛋白激酶(cdk8)相关联,有人提出这种复合物可能在细胞周期中调节RNA转录。此外,人类细胞周期蛋白C基因已定位到人类染色体6q21,并且发现它在一部分急性淋巴细胞白血病(ALL)中经常缺失。对禽T细胞cDNA文库进行筛选,分离出了一种细胞周期蛋白C同源物以及一种丰富但不同的细胞周期蛋白C相关cDNA。细胞周期蛋白C cDNA预测的开放阅读框(ORF)编码一个283个氨基酸的蛋白质,该蛋白质与人类蛋白质的同源性>99%,与黑腹果蝇蛋白质的同源性为72%。然而,细胞周期蛋白C相关cDNA预测的ORF编码一个小得多的105个氨基酸的蛋白质,该蛋白质在细胞周期蛋白框区域(氨基酸残基98)之前与细胞周期蛋白C完全相同,之后突然不同并终止。通过对一系列细胞系和组织来源的cDNA进行PCR分析,已证明禽细胞周期蛋白C基因存在可变剪接。此外,用细胞周期蛋白C特异性抗体在正常和病毒转化的禽细胞中检测到一种与体外转录和翻译的截短细胞周期蛋白C蛋白共迁移的约19 kDa的较小蛋白质。可变剪接的细胞周期蛋白C mRNA和蛋白质的表达以细胞周期依赖性方式受到调节,这与细胞周期蛋白B2类似。这种截短的细胞周期蛋白C蛋白的功能尚不清楚,但其在禽细胞中的表达表明这种截短的细胞周期蛋白C蛋白可能作为一种早期内源性编码的细胞周期蛋白C抑制剂发挥作用。