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

Haotian Zhao, Olivier Ayrault, Frederique Zindy, Jee Hae Kim, Martine F. Roussel

Research output: Contribution to journalArticle

110 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)722-727
Number of pages6
JournalGenes and Development
Volume22
Issue number6
DOIs
StatePublished - Mar 15 2008

Fingerprint

Medulloblastoma
Down-Regulation
Neurons
Bone and Bones
Hedgehogs
Proteins
Proteasome Endopeptidase Complex
Transcription Factors
Stem Cells
Genes
Therapeutics

Keywords

  • Atoh1/Math1
  • Bone morphogenic protein
  • Medulloblastoma
  • Mycn
  • Sonic hedgehog

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development. / Zhao, Haotian; Ayrault, Olivier; Zindy, Frederique; Kim, Jee Hae; Roussel, Martine F.

In: Genes and Development, Vol. 22, No. 6, 15.03.2008, p. 722-727.

Research output: Contribution to journalArticle

Zhao, Haotian ; Ayrault, Olivier ; Zindy, Frederique ; Kim, Jee Hae ; Roussel, Martine F. / Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development. In: Genes and Development. 2008 ; Vol. 22, No. 6. pp. 722-727.
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