Trouche D, Grigoriev M, Lenormand J L, Robin P, Leibovitch S A, Sassone-Corsi P, Harel-Bellan A
Laboratoire de Biologie des Tumeurs Humaines, CNRS URA 1156, Villejuif, France.
Nature. 1993 May 6;363(6424):79-82. doi: 10.1038/363079a0.
Terminal differentiation and cell proliferation are in many cases, as in muscle cells, mutually exclusive processes. While differentiating myoblasts are withdrawn from the cell cycle, myogenesis is inhibited by some mitogens and overexpression of some oncogenes, including proto-oncogene c-fos (which expresses a growth-associated protein constituting the regulatory factor AP-1 in conjunction with c-Jun). MyoD, a muscle-specific transcription factor of the basic helix-loop-helix family, acts at both levels because it triggers a muscle differentiation programme in non-muscle cells, and induces a complete block of cell proliferation. Antagonistic interaction between MyoD and c-Jun has been demonstrated. We here show that c-fos expression greatly decreases upon muscle cell differentiation, concomitant with MyoD-induced activity. We have identified a MyoD-binding site overlapping with the serum-responsive element in the c-fos promoter. We demonstrate that MyoD can act as a negative regulator for c-fos transcription by blocking serum responsiveness through this binding site. These data suggest that the MyoD negative effect on cell growth could be partly mediated by transcriptional inactivation of growth-responsive genes.
在许多情况下，如在肌肉细胞中，终末分化和细胞增殖是相互排斥的过程。当分化中的成肌细胞退出细胞周期时，肌生成会受到一些有丝分裂原和某些癌基因（包括原癌基因c-fos，它表达一种与生长相关的蛋白质，与c-Jun共同构成调节因子AP-1）过表达的抑制。MyoD是一种属于碱性螺旋-环-螺旋家族的肌肉特异性转录因子，在两个层面发挥作用，因为它能在非肌肉细胞中触发肌肉分化程序，并诱导细胞增殖的完全阻滞。已证明MyoD与c-Jun之间存在拮抗相互作用。我们在此表明，在肌肉细胞分化时，c-fos表达大幅下降，这与MyoD诱导的活性相伴。我们在c-fos启动子中鉴定出一个与血清反应元件重叠的MyoD结合位点。我们证明MyoD可通过该结合位点阻断血清反应性，从而作为c-fos转录的负调节因子发挥作用。这些数据表明，MyoD对细胞生长的负面影响可能部分是由生长反应基因的转录失活介导的。
