CORRELATION OF TERMINAL CELL-CYCLE ARREST OF SKELETAL-MUSCLE WITH INDUCTION OF P21 BY MYOD
CORRELATION OF TERMINAL CELL-CYCLE ARREST OF SKELETAL-MUSCLE WITH INDUCTION OF P21 BY MYOD
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DOI：
10.1126/science.7863327
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发表时间：
1995-02-17
期刊：
影响因子：
56.9
通讯作者：
LASSAR, AB
中科院分区：
文献类型：
--
作者：
HALEVY, O;NOVITCH, BG;LASSAR, AB
骨骼肌的分化需要协调肌肉特异性基因的表达，并最终退出细胞周期。这种细胞周期停滞在G(0)期需要视网膜母细胞瘤肿瘤抑制蛋白(Rb)。Rb的功能受细胞周期蛋白依赖性激酶(CDK)的负性调节，CDK受CDK抑制剂的控制。在小鼠肌细胞和非肌源性细胞分化过程中，骨骼肌特异性转录调节因子MyoD的表达激活了CDK抑制因子p21的表达。MyoD介导的p21的诱导不需要肿瘤抑制蛋白P53，并且与细胞周期退出有关。因此，MyoD可能通过增加p21的表达来诱导骨骼肌分化过程中细胞周期的终末停滞。
Skeletal muscle differentiation entails the coordination of muscle-specific gene expression and terminal withdrawal from the cell cycle. This cell cycle arrest in the G(0) phase requires the retinoblastoma tumor suppressor protein (Rb). The function of Rb is negatively regulated by cyclin-dependent kinases (Cdks), which are controlled by Cdk inhibitors. Expression of MyoD, a skeletal muscle-specific transcriptional regulator, activated the expression of the Cdk inhibitor p21 during differentiation of murine myocytes and in nonmyogenic cells. MyoD-mediated induction of p21 did not require the tumor suppressor protein p53 and correlated with cell cycle withdrawal. Thus, MyoD may induce terminal cell cycle arrest during skeletal muscle differentiation by increasing the expression of p21.