Hepsin inhibits CDK11p58 IRES activity by suppressing unr expression and eIF-2alpha phosphorylation in prostate cancer
Hepsin inhibits CDK11p58 IRES activity by suppressing unr expression and eIF-2alpha phosphorylation in prostate cancer
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Hepsin 通过抑制前列腺癌中 unr 表达和 eIF-2α 磷酸化来抑制 CDK11p58 IRES 活性
DOI：
10.1016/j.cellsig.2014.12.020
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发表时间：
2015
影响因子：
4.8
通讯作者：
Gu Jianxin
中科院分区：
文献类型：
--
作者：
Zhang Chunyi;Zhang Mingming;Wu Qingyu;Peng Jianhao;Ruan Yuanyuan;Gu Jianxin
Hepsin是一种II型跨膜丝氨酸蛋白酶，经常在前列腺癌（PCa）中过表达。然而，hepsin在PCa中的作用仍不清楚。在这项研究中，我们发现hepsin抑制内部核糖体进入位点（IRES）的活性和CDK 11 p58的表达，这与细胞周期进程和促凋亡信号在PCa。Hepsin通过调节unr表达和eIF-2α磷酸化抑制PCa中CDK 11 p58 IRES活性。进一步研究发现，hepsin通过直接与unr IRES元件结合并抑制其活性，抑制unr的表达，同时通过下调一般对照非去阻遏蛋白-2（GCN 2）的表达和磷酸化，抑制eIF-2α的磷酸化。两者合计，我们的数据表明，一种新的作用，hepsin在调节CDK 11 p58 IRES活性，并暗示，hepsin可能会采取行动的翻译机制，以调节细胞周期的进展和生存在前列腺癌细胞。
Hepsin is a type II transmembrane serine protease frequently overexpressed in prostate cancer (PCa). However, the role of hepsin in PCa remains unclear. In this study, we found that hepsin inhibited the internal ribosome entry site (IRES) activity and expression of CDK11p58, which is associated with cell cycle progression and pro-apoptotic signaling in PCa. Hepsin suppressed CDK11p58 IRES activity in PCa by modulating unr expression and eIF-2α phosphorylation. Further studies revealed that hepsin inhibited the expression of unr by directly binding to unr IRES element and suppressing its activity, and also repressed eIF-2α phosphorylation through down-regulating the expression and phosphorylation of general control non-derepressible-2 (GCN2). Taken together, our data suggest a novel role of hepsin in regulating CDK11p58 IRES activity, and imply that hepsin may act on the machinery of translation to modulate cell cycle progression and survival in PCa cells.