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HCF中的单点突变导致温度敏感的细胞周期停滞并破坏VP16功能。

A single-point mutation in HCF causes temperature-sensitive cell-cycle arrest and disrupts VP16 function.

作者信息

Goto H, Motomura S, Wilson A C, Freiman R N, Nakabeppu Y, Fukushima K, Fujishima M, Herr W, Nishimoto T

机构信息

Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka, Japan.

出版信息

Genes Dev. 1997 Mar 15;11(6):726-37. doi: 10.1101/gad.11.6.726.

DOI:10.1101/gad.11.6.726
PMID:9087427
Abstract

The temperature-sensitive BHK21 hamster cell line tsBN67 ceases to proliferate at the nonpermissive temperature after a lag of one to a few cell divisions, and the arrested cells display a gene expression pattern similar to that of serum-starved cells. The temperature-sensitive phenotype is reversible and results from a single missense mutation--proline to serine at position 134--in HCF, a cellular protein that, together with the viral protein VP16, activates transcription of herpes simplex virus (HSV) immediate-early genes. The tsBN67 HCF mutation also prevents VP16 activation of transcription at the nonpermissive temperature. The finding that the same point mutation in HCF disrupts both VP16 function and the cell cycle suggests that HCF plays a role in cell-cycle progression in addition to VP16-dependent transcription.

摘要

温度敏感型BHK21仓鼠细胞系tsBN67在一个到几个细胞分裂的延迟后,在非允许温度下停止增殖,并且停滞的细胞显示出与血清饥饿细胞相似的基因表达模式。这种温度敏感表型是可逆的,是由HCF中的单个错义突变导致的,即第134位的脯氨酸突变为丝氨酸,HCF是一种细胞蛋白,它与病毒蛋白VP16一起激活单纯疱疹病毒(HSV)立即早期基因的转录。tsBN67 HCF突变也会阻止VP16在非允许温度下激活转录。HCF中相同的点突变破坏了VP16功能和细胞周期这一发现表明,HCF除了在依赖VP16的转录中发挥作用外,还在细胞周期进程中发挥作用。

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