State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Biochim Biophys Acta Gene Regul Mech. 2017 Apr;1860(4):516-522. doi: 10.1016/j.bbagrm.2017.02.006. Epub 2017 Feb 21.
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.
CR6 相互作用因子 1（CRIF1）在人体组织中广泛表达。CRIF1 最初被鉴定为 Gadd45γ（也称为 CR6）相互作用蛋白，并且在 p53 稳定转化的人结肠癌细胞系中也被鉴定出来。这些结果表明，CRIF1 在细胞核中与 p53 和 Gadd45 家族蛋白一起抑制细胞生长和肿瘤发生。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，从而增加 p53 的 mRNA 和蛋白水平以及 p53 功能靶基因。这些功能需要 CRIF1 与 SNF5 相互作用。CRIF1 进一步被募集到 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，这是第一个表明 SNF5 对于 CRIF1 增强 p53 活性及其在抑制人类癌细胞周期停滞中的功能是必不可少的证据。
