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

Oncogene. 2006 Aug 28;25(38):5244-9. doi: 10.1038/sj.onc.1209623.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Communication
  • Cell Cycle / physiology*
  • Cell Differentiation / physiology*
  • Genes, Retinoblastoma*
  • Humans
  • Muscle, Skeletal / physiology*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / physiology*
  • Signal Transduction
  • Transcription, Genetic


  • Retinoblastoma Protein