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 language | English |
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Pages (from-to) | 5244-5249 |
Number of pages | 6 |
Journal | Oncogene |
Volume | 25 |
Issue number | 38 |
DOIs | |
Publication status | Published - Aug 28 2006 |
Keywords
- Cell cycle withdrawal
- Differentiation
- MyoD
- Myogenesis
- Retinoblastoma gene
- Tissue-specific transcription
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics