Endoplasmic reticulum stress inhibits cell cycle progression via induction of p27 in melanoma cells
Endoplasmic reticulum stress inhibits cell cycle progression via induction of p27 in melanoma cells
复制标题
内质网应激通过诱导黑色素瘤细胞中的 p27 抑制细胞周期进程。
DOI：
10.1016/j.cellsig.2012.09.023
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发表时间：
2013-01-01
影响因子：
4.8
通讯作者：
Wu, Mian
中科院分区：
文献类型：
--
作者：
Han, Chuanchun;Jin, Lei;Wu, Mian
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), a stress signaling pathway. The UPR coordinates the induction of ER chaperones with decreased protein synthesis and growth arrest in G1 phase of the cell cycle. However, the molecular mechanism underlying UPR-induced G1 cell cycle arrest remains largely unknown. Here we report that activation of the UPR response by tunicamycin (TM), an ER stress inducer, leads to accumulation of p27 and G1 cell cycle arrest in melanoma cells. This accumulation of p27 is due to the inhibition on its polyubiquitination and subsequent degradation upon TM treatment. Correlated with p27 stabilization, the levels of Skp2, an E3 ligase for p27, are decreased in response to TM treatment More importantly, knockdown of p27 greatly reduces TM-induced G1 cell cycle arrest. Taken together, these data implicate p27 as a critical mediator of ER stress-induced growth arrest. (C) 2012 Elsevier Inc. All rights reserved.
