De Falco G, Comes F, Simone C
Department of Human Pathology and Oncology, University of Siena, Siena, Italy.
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.
视网膜母细胞瘤（RB）基因的蛋白质产物对于肌肉分化程序的完成以及对成肌碱性螺旋-环-螺旋依赖性转录而言是必需的。事实上，除了通过对参与增殖的E2F反应基因进行负调控来诱导和维持永久性细胞周期停滞外，pRb在肌肉特异性基因的激活中也发挥着积极作用。在pRb基因敲除的肌细胞中，晚期成肌标志物的表达存在缺陷，成肌细胞融合形成肌管时并未发生不可逆的细胞周期退出。这一证据仅表明pRb与其相关蛋白p107和pRb2/p130之间存在部分功能冗余，因为这些pRb基因敲除的多核细胞显示p107水平高于正常肌管，它们对有丝分裂原的反应是重新进入细胞周期并进行DNA合成。在分子水平上，pRb的成肌功能是通过与MyoD、肌细胞增强因子2（MEF2）、高迁移率族蛋白1（HBP1）和组蛋白去乙酰化酶1合作来介导的，这些合作会影响染色质构型和组织特异性转录，并且通过响应细胞内信号级联反应的翻译后修饰来实现。
