MDMX inhibits Casein Kinase 1? activity and stimulates Wnt signaling

ABSTRACT: Casein kinase 1 alpha (CK1?) is a serine/threonine kinase with numerous functions, including regulating the Wnt/?-catenin and p53 pathways. CK1? 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 CK1?, suggesting that MDMX may in turn regulate CK1? function. We present evidence that MDMX is a potent competitive inhibitor of CK1? kinase activity (Ki=8 nM). Depletion of MDMX increases CK1? activity and ?-catenin S45 phosphorylation, whereas ectopic MDMX expression inhibits CK1? activity and ?-catenin phosphorylation. The MDMX acidic domain and zinc finger are necessary and sufficient for binding and inhibition of CK1?. P53 binding to MDMX disrupts an intra

SUBMITTER: Prof. Jiandong Chen 

PROVIDER: S-SCDT-EMBOJ-2020-104410 | biostudies-other |

REPOSITORIES: biostudies-other