IL-1-induced ERK1/2 activation up-regulates p21Waf1/Cip1 protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375
IL-1-induced ERK1/2 activation up-regulates p21Waf1/Cip1 protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375
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DOI：
10.1016/j.bbrc.2010.01.027
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发表时间：
2010-02-12
影响因子：
3.1
通讯作者：
Onozaki, Kikuo
中科院分区：
文献类型：
--
作者：
Arakawa, Tomohiro;Hayashi, Hidetoshi;Onozaki, Kikuo
IL-1通过将细胞周期阻滞在G 0/G1期来抑制人黑色素瘤细胞A375的增殖，这伴随着IL-1的增加21（Waf 1/cip 1）（P21）蛋白在此，我们证明IL-1通过ERK 1/2途径诱导p21蛋白的稳定化。IL-1抑制p21的降解，但不影响p21的泛素化水平。此外，IL-1抑制p21-K6 R非泛素化形式的降解，提示IL-1通过非泛素依赖性途径稳定p21蛋白。此外，ERK 1/2通路的选择性抑制剂PD 98059阻止了对p21蛋白降解的抑制。这些结果表明，IL-1诱导的ERK 1/2活化通过抑制人黑素瘤细胞A375中经由泛素非依赖性通路的降解而导致p21的上调。版权所有
IL-1 inhibits the proliferation of human melanoma cells A375 by arresting the cell cycle at G0/G1 phase, which accompanies the increase 21(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 (C) 2010 Elsevier Inc. All rights reserved