INTERACTION OF MYOGENIC FACTORS AND THE RETINOBLASTOMA PROTEIN MEDIATES MUSCLE-CELL COMMITMENT AND DIFFERENTIATION
INTERACTION OF MYOGENIC FACTORS AND THE RETINOBLASTOMA PROTEIN MEDIATES MUSCLE-CELL COMMITMENT AND DIFFERENTIATION
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DOI：
10.1016/0092-8674(93)90110-c
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发表时间：
1993-02-12
期刊：
影响因子：
64.5
通讯作者：
NADALGINARD, B
中科院分区：
文献类型：
--
作者：
GU, W;SCHNEIDER, JW;NADALGINARD, B
本文报道的实验证明，肿瘤抑制视网膜母细胞瘤蛋白（pRB）在肌肉细胞终末分化表型的产生和维持中起重要作用。我们发现，通过磷酸化、与T抗原结合或基因改变，pRB失活可抑制肌生成。此外，在终末分化的细胞中，pRB的失活使它们能够重新进入细胞周期。除了参与MyoD的肌生成活动外，pRB也是这种肌生成因子的细胞生长抑制活性所必需的。我们还发现，在体内和体外，pRB和MyoD分别通过一个涉及口袋和基本螺旋-环-螺旋结构域的区域直接相互结合。所有结果都与MyoD对细胞周期的影响和pRB对肌生成途径的影响是由两种分子的直接结合引起的。
The experiments reported here document that the tumor suppressor retinoblastoma protein (pRB) plays an important role in the production and maintenance of the terminally differentiated phenotype of muscle cells. We show that pRB inactivation, through either phosphorylation, binding to T antigen, or genetic alteration, inhibits myogenesis. Moreover, inactivation of pRB in terminally differentiated cells allows them to reenter the cell cycle. In addition to its involvement in the myogenic activities of MyoD, pRB is also required for the cell growth-inhibitory activity of this myogenic factor. We also show that pRB and MyoD directly bind to each other, both in vivo and in vitro, through a region that involves the pocket and the basic-helix-loop-helix domains, respectively. All the results obtained are consistent with the proposal that the effects of MyoD on the cell cycle and of pRB on the myogenic pathway result from the direct binding of the two molecules.