Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development
- 15 March 2008
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 22 (6), 722-727
- https://doi.org/10.1101/gad.1636408
Abstract
Bone morphogenic proteins 2 and 4 (BMP2 and BMP4) inhibit proliferation and induce differentiation of cerebellar granule neuron progenitors (GNPs) and primary GNP-like medulloblastoma (MB) cells. This occurs through rapid proteasome-mediated degradation of Math1 (Atoh1), a transcription factor expressed in proliferating GNPs. Ectopic expression of Atoh1, but not of Sonic hedgehog (Shh)-regulated Gli1 or Mycn, cancels these BMP-mediated effects and restores Shh-dependent proliferation of GNPs and MB cells in vitro and in vivo. Genes regulating the BMP signaling pathway are down-regulated in mouse MBs. Thus, BMPs are potent inhibitors of MB and should be considered as novel therapeutic agents.Keywords
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