pRb: Master of differentiation. Coupling irreversible cell cycle withdrawal with induction of muscle-specific transcription

G. De Falco, F. Comes, C. Simone

Research output: Contribution to journalArticlepeer-review

Abstract

The protein product of the retinoblastoma (RB) gene is necessary for the completion of the muscle differentiation program and for myogenic basic helix-loop-helix-dependent transcription. In fact, in addition to induction and maintenance of permanent cell cycle withdrawal through negative regulation of E2F-responsive genes involved in proliferation, pRb also plays a positive role in the activation of muscle-specific genes. In pRb-/- myocytes, the expression of late myogenic markers is defective and myoblast fusion into myotubes occurs without irreversible cell cycle exit. This evidence demonstrates only a partial functional redundancy between pRb and its relatives p107 and pRb2/p130, as these pRb-/- multinucleated cells, which display p107 levels higher than normal myotubes, respond to mitogens with cell cycle re-entry and DNA synthesis. At the molecular level, pRb myogenic functions are mediated by cooperation with MyoD, Myocyte enhancer factor 2 (MEF2), High mobility group box protein-1 (HBP1) and histone deacetylase1, affecting chromatin configuration and tissue-specific transcription, and by post-translational modification in response to intracellular signaling cascades.

Original languageEnglish
Pages (from-to)5244-5249
Number of pages6
JournalOncogene
Volume25
Issue number38
DOIs
Publication statusPublished - Aug 28 2006

Keywords

  • Cell cycle withdrawal
  • Differentiation
  • MyoD
  • Myogenesis
  • Retinoblastoma gene
  • Tissue-specific transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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