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Cell Signal. 2015 Apr;27(4):789-97. doi: 10.1016/j.cellsig.2014.12.020. Epub 2015 Jan 7.

Hepsin inhibits CDK11p58 IRES activity by suppressing unr expression and eIF-2α phosphorylation in prostate cancer.

Author information

1
Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
2
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
3
Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yuanyuanruan@fudan.edu.cn.

Abstract

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.

KEYWORDS:

CDK11p58; Hepsin; IRES; eIF-2α; unr

PMID:
25576733
DOI:
10.1016/j.cellsig.2014.12.020
[Indexed for MEDLINE]

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