RNF6 promotes cell proliferation of glioblastoma by targeting ubiquitin-mediated degradation of p27

Abstract

RNF6 (RING finger protein 6), an atypical RING-type ubiquitin ligase, has been reported to be a potential tumor promoter in several human cancers. However, the role of RNF6 in glioblastoma remains poorly understood. In this study, we found that RNF6 was highly expressed in glioblastoma tissues, and its elevated expression was significantly associated with poor prognosis in glioblastoma patients. RNF6 depletion remarkably inhibited cell growth of glioblastoma cells. Mechanistically, RNF6 depletion stabilized p27 protein expression. We demonstrated that RNF6 interacted with p27 and mediated its ubiquitination and degradation in an E3 ligase activity-dependent manner. Moreover, we provide the first evidence revealing the crucial role RNF6 in mediating SKP2 expression at both transcriptional and post-translational levels. On the one hand, RNF6 played as a transcription factor to regulate the activity of the SKP2 promoter. On the other hand, RNF6 interacted with SKP2 and stabilized its protein levels in an Akt-dependent manner. Collectively, our data indicated that RNF6 accelerated glioblastoma cell proliferation and tumorigenesis by targeting p27 for degradation.