Tuberous sclerosis complex suppression in cerebellar development and medulloblastoma: separate regulation of mammalian target of rapamycin activity and p27 Kip1 localization.

ABSTRACT: During development, proliferation of cerebellar granule neuron precursors (CGNP), candidate cells-of-origin for the pediatric brain tumor medulloblastoma, requires signaling by Sonic hedgehog (Shh) and insulin-like growth factor (IGF), the pathways of which are also implicated in medulloblastoma. One of the consequences of IGF signaling is inactivation of the mammalian target of rapamycin (mTOR)-suppressing tuberous sclerosis complex (TSC), comprised of TSC1 and TSC2, leading to increased mRNA translation. We show that mice, in which TSC function is impaired, display increased mTOR pathway activation, enhanced CGNP proliferation, glycogen synthase kinase-3 alpha/beta (GSK-3 alpha/beta) inactivation, and cytoplasmic localization of the cyclin-dependent kinase inhibitor p27(Kip1), which has

SUBMITTER: Bhatia B 

PROVIDER: S-EPMC2745891 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature