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