Calcineurin-mediated dephosphorylation enhances the stability and transactivation of c-Myc.

ABSTRACT: c-Myc, a transcription factor, induces cell proliferation and is often aberrantly or highly expressed in cancers. However, molecular mechanisms underlying this aberrantly high expression remain unclear. Here, we found that intracellular Ca²⁺ concentration regulates c-Myc oncoprotein stability. We identified that calcineurin, a Ca²⁺-dependent protein phosphatase, is a positive regulator of c-Myc expression. Calcineurin depletion suppresses c-Myc targeted gene expression and c-Myc degradation. Calcineurin directly dephosphorylates Thr⁵⁸ and Ser⁶² in c-Myc, which inhibit binding to the ubiquitin ligase Fbxw7. Mutations within the autoinhibitory domain of calcineurin, most frequently observed in cancer, may increase phosphatase activity, increasing c

SUBMITTER: Masaki T 

PROVIDER: S-EPMC10423207 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature