Wang J, Guo K, Wills K N, Walsh K
Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
Cancer Res. 1997 Feb 1;57(3):351-4.
During in vitro myogenesis, a portion of myoblasts undergo apoptosis, whereas others continue with their differentiation program and form myotubes that are resistant to cell death. Previous work has shown that the expression of the Cdk inhibitor p21 correlates with enhanced resistance to apoptosis and that forced expression of p21 will confer this phenotype on differentiating myocytes. Here we examine the role of the retinoblastoma gene (Rb) in myocyte survival. Compared with wild-type myocytes, CC42 (Rb-/-) myocytes undergo higher frequencies of apoptosis during mitogen deprivation-induced myogenesis. Despite these features, Rb-/- myocytes display normal up-regulation of p21 and down-regulation of Cdk activities upon differentiation. Adenoviral constructs expressing the Cdk inhibitors p21 or p16 inhibit apoptosis in wild-type but not Rb-/- myocyte cultures. On the other hand, a Rb-expressing adenoviral construct inhibited apoptosis in both cell types. These data demonstrate that Rb functions downstream from the Cdk inhibitors to coordinate cell cycle withdrawal with programmed cell death during myocyte differentiation.
在体外成肌过程中，一部分成肌细胞会发生凋亡，而其他细胞则继续其分化程序并形成对细胞死亡具有抗性的肌管。先前的研究表明，细胞周期蛋白依赖性激酶（Cdk）抑制剂p21的表达与增强的抗凋亡能力相关，并且强制表达p21会使分化中的心肌细胞具有这种表型。在此，我们研究视网膜母细胞瘤基因（Rb）在心肌细胞存活中的作用。与野生型心肌细胞相比，CC42（Rb-/-）心肌细胞在有丝分裂原剥夺诱导的成肌过程中经历更高频率的凋亡。尽管有这些特征，但Rb-/-心肌细胞在分化时仍表现出正常的p21上调和Cdk活性下调。表达Cdk抑制剂p21或p16的腺病毒构建体可抑制野生型而非Rb-/-心肌细胞培养物中的凋亡。另一方面，表达Rb的腺病毒构建体可抑制两种细胞类型中的凋亡。这些数据表明，Rb在Cdk抑制剂的下游发挥作用，以在心肌细胞分化过程中协调细胞周期退出与程序性细胞死亡。
