CRIF1 enhances p53 activity via the chromatin remodeler SNF5 in the HCT116 colon cancer cell lines
CRIF1 enhances p53 activity via the chromatin remodeler SNF5 in the HCT116 colon cancer cell lines
复制标题
CRIF1 通过 HCT116 结肠癌细胞系中的染色质重塑因子 SNF5 增强 p53 活性
DOI：
10.1016/j.bbagrm.2017.02.006
复制
发表时间：
2017
影响因子：
4.7
通讯作者：
Zhang Ye
中科院分区：
文献类型：
--
作者：
Yan Hai-xia;Zhang Yan-jun;Zhang Yuan;Ren Xue;Shen Yu-fei;Cheng Mo-bin;Zhang Ye
CR6相互作用因子1(CRIF1)在人体组织中广泛表达。CRIF1首先被鉴定为GADD45CR6(也称为γ)相互作用蛋白，也在稳定转化P53的人结肠癌细胞系中被鉴定。这些结果表明，CRIF1与P53和GADD45家族蛋白一起在细胞核内发挥作用，抑制细胞生长和肿瘤的发展。在这里，我们发现CRIF1可以被募集到p53基因启动子的特定区域，引起P53和P53功能靶基因的mRNA和蛋白水平的增加。这些功能需要CRIF1与SNF5相互作用。CRIF1被进一步招募到p53基因的上游启动子区域，以抑制HCT116细胞的细胞周期进程。据我们所知，这是第一个证据表明SNF5对于CRIF1增强的P53活性及其在抑制人癌细胞细胞周期停滞中的作用是不可或缺的。
CR6-interacting factor 1 (CRIF1) is ubiquitously expressed in human tissues. CRIF1 was first identified as a Gadd45γ (also known as CR6)-interacting protein, and it was also identified in a human colon cancer cell line stably transformed with p53. These results suggested that CRIF1 functions in the nucleus with p53 and Gadd45 family proteins in the suppression of cell growth and tumor development. Here, we found that CRIF1 could be recruited to a specific region in the promoter of the p53 gene, eliciting an increase in the mRNA and protein levels of p53 as well as p53 functional target genes. These functions required CRIF1 to interact with SNF5. CRIF1 was further recruited to the upstream promoter region of the p53 gene to suppress cell cycle progression in HCT116 cells. To our knowledge, this is the first evidence indicating that SNF5 is indispensable for CRIF1-enhanced p53 activity and its function in the suppression of cell cycle arrest in human cancer cells.