CRY2 missense mutations suppress P53 and enhance cell growth
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
下载链接：
http://data.iscr.ac.cn/Article?id=b678014867e0901680819fc4b5a3f8de
下载链接
链接失效反馈官方服务：
资源简介：
Disruption of circadian rhythms increases the risk of several types of cancer. Mammalian cryptochromes (CRY1 and CRY2) are circadian transcriptional repressors that are related to DNA repair enzymes. While CRYs lack DNA repair activity, they modulate the transcriptional response to DNA damage, and CRY2 can promote SCFFBXL3-mediated ubiquitination of c-MYC and other targets. Here, we characterize five mutations in CRY2 observed in human cancers in The Cancer Genome Atlas. We demonstrate that two orthologous mutations of mouse CRY2 (D325H and S510L) accelerate the growth of primary mouse fibroblasts expressing high levels of c-MYC. Neither mutant affects steady state levels of overexpressed c-MYC, and they have divergent impacts on circadian rhythms and on the ability of CRY2 to interact with SCFFBXL3. Unexpectedly, stable expression of either CRY2 D325H or of CRY2 S510L robustly suppresses P53 target gene expression, suggesting that this is the primary mechanism by which they influence cell growth.
提供机构：
Scripps Research
创建时间：
2022-02-20
