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

doi:10.1101/gad.1636408

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 journal › Article › peer-review

126 Scopus citations

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 language	English (US)
Pages (from-to)	722-727
Number of pages	6
Journal	Genes and Development
Volume	22
Issue number	6
DOIs	https://doi.org/10.1101/gad.1636408
State	Published - Mar 15 2008
Externally published	Yes

Keywords

Atoh1/Math1
Bone morphogenic protein
Medulloblastoma
Mycn
Sonic hedgehog

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.1636408

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title = "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.",

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AU - Zhao, Haotian

AU - Ayrault, Olivier

AU - Zindy, Frederique

AU - Kim, Jee Hae

AU - Roussel, Martine F.

PY - 2008/3/15

Y1 - 2008/3/15

N2 - 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.

AB - 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.

KW - Atoh1/Math1

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KW - Medulloblastoma

KW - Mycn

KW - Sonic hedgehog

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

Abstract

Keywords

ASJC Scopus subject areas

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