MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling.

ABSTRACT: Casein kinase 1 alpha (CK1α) is a serine/threonine kinase with numerous functions, including regulating the Wnt/β-catenin and p53 pathways. CK1α has a well-established role in inhibiting the p53 tumor suppressor by binding to MDMX and stimulating MDMX-p53 interaction. MDMX purified from cells contains near-stoichiometric amounts of CK1α, suggesting that MDMX may in turn regulate CK1α function. We present evidence that MDMX is a potent competitive inhibitor of CK1α kinase activity (K_i  = 8 nM). Depletion of MDMX increases CK1α activity and β-catenin S45 phosphorylation, whereas ectopic MDMX expression inhibits CK1α activity and β-catenin phosphorylation. The MDMX acidic domain and zinc finger are necessary and sufficient for binding and inhibition of CK1α. P53 binding to MDMX dis

SUBMITTER: Huang Q 

PROVIDER: S-EPMC7361285 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature