LncRNAs-directed PTEN enzymatic switch governs epithelial-mesenchymal transition.

ABSTRACT: Despite the structural conservation of PTEN with dual-specificity phosphatases, there have been no reports regarding the regulatory mechanisms that underlie this potential dual-phosphatase activity. Here, we report that K27-linked polyubiquitination of PTEN at lysines 66 and 80 switches its phosphoinositide/protein tyrosine phosphatase activity to protein serine/threonine phosphatase activity. Mechanistically, high glucose, TGF-β, CTGF, SHH, and IL-6 induce the expression of a long non-coding RNA, GAEA (Glucose Aroused for EMT Activation), which associates with an RNA-binding E3 ligase, MEX3C, and enhances its enzymatic activity, leading to the K27-linked polyubiquitination of PTEN. The MEX3C-catalyzed PTEN^K27-polyUb activates its protein serine/threonine phosphatase activity an

SUBMITTER: Hu Q 

PROVIDER: S-EPMC6461864 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature