p53 regulates myogenesis by triggering the differentiation activity of pRb.
p53 regulates myogenesis by triggering the differentiation activity of pRb.
复制标题
DOI：
10.1083/jcb.151.6.1295
复制
发表时间：
2000-12-11
期刊：
影响因子：
--
通讯作者：
Soddu S
中科院分区：
文献类型：
--
作者：
Porrello A;Cerone MA;Coen S;Gurtner A;Fontemaggi G;Cimino L;Piaggio G;Sacchi A;Soddu S
P53癌抑制蛋白调节细胞周期检查点和细胞凋亡，但越来越多的证据表明它也参与了分化和发育。我们以前已经证明，在分化促进刺激的存在下，p53缺陷的成肌细胞退出细胞周期，但不能分化为肌细胞和肌管。为了确定P53促进骨骼肌分化的途径，我们分析了在肌肉发生过程中调节的一系列基因在亲代和表达显性负P53(DnP53)的C2C12成肌细胞中的表达。我们发现，在表达dnP53的C2C12细胞中，以及在P53−/−原代成肌细胞中，pRb被低磷酸化，增殖停止。然而，这些细胞不上调pRB，并降低了MyoD的活性。外源TP53或Rb基因在p53缺陷成肌细胞中的转导挽救了MyoD的活性和分化潜能。此外，对Rb启动子的体内研究表明，P53通过P53结合位点在转录水平上调节Rb基因的表达。因此，我们在这里表明，P53通过pRB调节成肌细胞的分化，而不影响其细胞周期相关功能。
The p53 oncosuppressor protein regulates cell cycle checkpoints and apoptosis, but increasing evidence also indicates its involvement in differentiation and development. We had previously demonstrated that in the presence of differentiation-promoting stimuli, p53-defective myoblasts exit from the cell cycle but do not differentiate into myocytes and myotubes. To identify the pathways through which p53 contributes to skeletal muscle differentiation, we have analyzed the expression of a series of genes regulated during myogenesis in parental and dominant–negative p53 (dnp53)-expressing C2C12 myoblasts. We found that in dnp53-expressing C2C12 cells, as well as in p53−/− primary myoblasts, pRb is hypophosphorylated and proliferation stops. However, these cells do not upregulate pRb and have reduced MyoD activity. The transduction of exogenous TP53 or Rb genes in p53-defective myoblasts rescues MyoD activity and differentiation potential. Additionally, in vivo studies on the Rb promoter demonstrate that p53 regulates the Rb gene expression at transcriptional level through a p53-binding site. Therefore, here we show that p53 regulates myoblast differentiation by means of pRb without affecting its cell cycle–related functions.
登录
查看更多内容
影响因子：
56.9
作者：
HALEVY, O;NOVITCH, BG;LASSAR, AB
通讯作者：
LASSAR, AB
影响因子：
2.7
作者：
ALMON, E;GOLDFINGER, N;ROTTER, V
通讯作者：
ROTTER, V
DOI：
10.1073/pnas.88.14.6293
发表时间：
1991-07-01
影响因子：
11.1
作者：
FEINSTEIN, E;CIMINO, G;CANAANI, E
通讯作者：
CANAANI, E
影响因子：
64.5
作者：
GU, W;SCHNEIDER, JW;NADALGINARD, B
通讯作者：
NADALGINARD, B
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A