Nonsense-mediated decay factor SMG7 sensitizes cells to TNFα-induced apoptosis via CYLD tumor suppressor and the noncoding oncogene Pvt1.

ABSTRACT: Nonsense-mediated decay (NMD) proteins are responsible for the surveillance and degradation of aberrant RNAs. Suppressor with morphogenetic effect on genitalia 7 (SMG7) is an NMD complex protein and a regulator of tumor necrosis factor (TNF)-induced extrinsic apoptosis; however, this unique function has not been explored in detail. In this study, we show that loss of Smg7 leads to unrestricted expression of long noncoding RNAs (lncRNAs) in addition to NMD targets. Functional analysis of Smg7^-/- cells showed downregulation of the tumor suppressor cylindromatosis (CYLD) and diminished caspase activity, thereby switching cells to nuclear factor-κB (NF-κB)-mediated protection. This positive relationship between SMG7 and CYLD was found to be widely conserved in human cancer cell line

SUBMITTER: Yang L 

PROVIDER: S-EPMC7530794 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature