CHFR基因与消化道肿瘤关系的研究进展  

Advance in the relationship between checkpoint with fork head associated and ring finger gene and carcinomas of digestive tract

作　　者：高余佳[1] 辛彦[2] 

机构地区：[1]辽宁省肿瘤医院内六科 [2]中国医科大学附属第一医院肿瘤研究所第四研究室,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2007年第15期1745-1749,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金;No.30371607;教育部博士点专项基金;No.20040159021~~

摘　　要：CHFR(checkpoint with FHA and ring finger),一种在人类癌症中灭活的新的细胞周期检查点基因,在有丝分裂应激时,延迟染色体的浓集、阻止细胞进入有丝分裂中前期.研究表明,CHFR在爪蟾中是P1k1的泛素连接酶,在哺乳动物细胞中主要通过抑制Cyclin B_1进入细胞核、调节Aurora-A的水平及与P38应激激酶相互作用,阻止细胞进入有丝分裂前期.USP7介导的CHFR去泛素化致其累积可能对于CHFR激活是一个关键的调节步骤.在消化道肿瘤中,CHFR表达由于CPG岛甲基化而沉默.本文对CHFR基因的结构、编码蛋白的功能及其与消化道肿瘤关系的研究进展作一综述.CHFR （checkpoint with fork head associated and ring finger）, a novel checkpoint gene, was frequently inactivated in human cancers. In response to mitotic stress, it causes a delay in chromosome condensation during prophase. Studies have showed that the direct target of the CHFR pathway was P1k1. In vitro-translated P1k1 is ubiquitinated, in a CHFR-dependent manner, both in Xenopus interphase extracts as well as in a purified system reconstituted with recombinant proteins. In addition, by excluding Cyclin B1 from the nucleus, regulating Aurora-A level and acting with the P38 stress kinases, CHFR blocks entry to mitosis prophase in mammalian cells. Besides, USP7 can remove ubiquitin moiety from the autoubiquitinated CHFR both in vivo and in vitro, which results in the accumulation of CHFR in the cells. Thus, USP7-mediated deubiquitination of CHFR leads to its accumulation, which might be a key regulatory step for CHFR activation. CHFR expression is frequently silenced by aberrant methylation in the carcinomas of digestive tract. In this article, we reviewed the progress of research on the structure of CHFR gene and effect of CHFR protein as well as its relation to the carcinomas of digestive tract.

关 键 词：有丝分裂前期 细胞周期检查点 CHFR基因 消化道肿瘤 

分 类 号：R735[医药卫生—肿瘤]