Non-canonical Hedgehog/AMPK-Mediated Control of Polyamine Metabolism Supports Neuronal and Medulloblastoma Cell Growth.

ABSTRACT: Developmental Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs), and its aberrant activation is a leading cause of medulloblastoma. We show here that Hedgehog promotes polyamine biosynthesis in GCPs by engaging a non-canonical axis leading to the translation of ornithine decarboxylase (ODC). This process is governed by AMPK, which phosphorylates threonine 173 of the zinc finger protein CNBP in response to Hedgehog activation. Phosphorylated CNBP increases its association with Sufu, followed by CNBP stabilization, ODC translation, and polyamine biosynthesis. Notably, CNBP, ODC, and polyamines are elevated in Hedgehog-dependent medulloblastoma, and genetic or pharmacological inhibition of this axis efficiently blocks Hedgehog-dependent proliferation of me

SUBMITTER: D'Amico D 

PROVIDER: S-EPMC4607931 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature