Liu Y, Hengartner M O, Herr W
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Mol Cell Biol. 1999 Jan;19(1):909-15. doi: 10.1128/MCB.19.1.909.
HCF is a mammalian nuclear protein that undergoes proteolytic processing and is required for cell proliferation. During productive herpes simplex virus (HSV) infection, the viral transactivator VP16 associates with HCF to initiate HSV gene transcription. Here, we show that the worm Caenorhabditis elegans possesses a functional homolog of mammalian HCF that can associate with and activate the viral protein VP16. The pattern of sequence conservation, however, is uneven. Sequences required for mammalian HCF processing are not present in C. elegans HCF. Furthermore, not all elements of mammalian HCF that are required for promoting cell proliferation are conserved. Nevertheless, unexpectedly, C. elegans HCF can promote mammalian cell proliferation because a region of HCF that is conserved can promote mammalian cell proliferation better than its human counterpart. These results suggest that HCF possesses a highly conserved role in metazoan cell proliferation which is targeted by VP16 to regulate HSV infection. The precise mechanisms, however, by which HCF functions in mammals and worms appear to differ.
HCF是一种哺乳动物核蛋白，它会经历蛋白水解加工，是细胞增殖所必需的。在单纯疱疹病毒（HSV）有效感染期间，病毒反式激活因子VP16与HCF结合以启动HSV基因转录。在此，我们表明线虫秀丽隐杆线虫拥有哺乳动物HCF的功能同源物，它可以与病毒蛋白VP16结合并激活它。然而，序列保守模式并不均匀。秀丽隐杆线虫HCF中不存在哺乳动物HCF加工所需的序列。此外，并非促进细胞增殖所需的所有哺乳动物HCF元件都是保守的。然而，出乎意料的是，秀丽隐杆线虫HCF可以促进哺乳动物细胞增殖，因为HCF的一个保守区域比其人类对应物更能促进哺乳动物细胞增殖。这些结果表明，HCF在后生动物细胞增殖中具有高度保守的作用，VP16靶向该作用来调节HSV感染。然而，HCF在哺乳动物和线虫中发挥作用的确切机制似乎有所不同。
