FAM175B promotes apoptosis by inhibiting ATF4 ubiquitination in esophageal squamous cell carcinoma

摘要: FAM175B is a reported regulator of p53 and suppresses tumorigenesis in numerous types cancer, but very little known about its function esophageal squamous cell carcinomas (ESCCs), almost 70% which exhibit mutations p53. Here, we report that expression downregulated high-grade intraepithelial neoplasia (t = 2.44, P 0.031) ESCC 5.664, < 0.001) tissues relative to adjacent normal tissues. Exogenous cells resulted decrease proliferation rate, inhibition colony formation, an increase apoptosis rate. Knockdown produced the opposite results. Furthermore, confocal microscopy coimmunoprecipitation assay showed Activating transcription factor 4 (ATF4) colocalized interacted with FAM175B. Ubiquitination assays revealed inhibited ubiquitin-dependent ATF4 degradation elevated protein level. Finally, luciferase reporter experiments further clarified promoted CHOP ATF4-dependent manner. Accordingly, proapoptotic activity was significantly rescued by treatment si-ATF4 inhibitor 4-PBA. In summary, ubiquitination p53-independent loss may be early diagnostic biomarker patients.