Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Biochem Biophys Res Commun. 2010 Feb 12;392(3):369-72. doi: 10.1016/j.bbrc.2010.01.027. Epub 2010 Jan 13.
IL-1 inhibits the proliferation of human melanoma cells A375 by arresting the cell cycle at G0/G1 phase, which accompanies the increase of p21(Waf1/Cip1) (p21) protein. Here, we demonstrate that IL-1 induces the stabilization of p21 protein via ERK1/2 pathway. The degradation of p21 was inhibited by IL-1, however the ubiquitination level of p21 was not affected. In addition, the degradation of non-ubiquitinated form of lysine less mutant p21-K6R was also inhibited by IL-1, suggesting that IL-1 stabilized p21 protein via ubiquitin-independent pathway. Furthermore, the inhibition of p21 protein degradation was prevented by a selective inhibitor of ERK1/2 pathway, PD98059. These results suggest that IL-1-induced ERK1/2 activation leads to the up-regulation of p21 by inhibiting degradation via ubiquitin-independent pathway in human melanoma cells A375.
IL-1 通过将细胞周期阻滞在 G0/G1 期来抑制人黑色素瘤细胞 A375 的增殖，伴随 p21(Waf1/Cip1) (p21) 蛋白的增加。在这里，我们证明 IL-1 通过 ERK1/2 途径诱导 p21 蛋白的稳定。IL-1 抑制了 p21 的降解，然而 p21 的泛素化水平没有受到影响。此外，非泛素化形式的赖氨酸残基更少的突变体 p21-K6R 的降解也被 IL-1 抑制，表明 IL-1 通过非泛素依赖途径稳定了 p21 蛋白。此外，ERK1/2 途径的选择性抑制剂 PD98059 可防止 p21 蛋白降解的抑制。这些结果表明，IL-1 诱导的 ERK1/2 激活通过非泛素依赖途径抑制降解，导致人黑色素瘤细胞 A375 中 p21 的上调。
