Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development.

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Zhao H,Ayrault O,Zindy F,Kim JH,Roussel MF

doi

10.1101/gad.1636408

subject

Has Abstract

pub_date

2008-03-15 00:00:00

pages

722-7

issue

6

eissn

0890-9369

issn

1549-5477

pii

22/6/722

journal_volume

22

pub_type

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