TGF-β1 accelerates the DNA damage response in epithelial cells via Smad signaling

被引：24

作者：

Lee, Jeeyong ^{[1
]}

Kim, Mi-Ra ^{[1
]}

Kim, Hyun-Ji ^{[1
]}

An, You Sun ^{[1
]}

Yi, Jae Youn ^{[1
]}

机构：

[1] Korea Inst Radiat & Med Sci, Div Basic Radiat Biosci, 75 Nowon Gil, Seoul 01812, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2016年 / 476卷 / 04期

关键词：

TGF-beta; 1; DNA damage response; Smads; Lig4; Radioprotection; GROWTH-FACTOR-BETA; ATM; KINASE; REPAIR; INHIBITION; ACTIVATION; RADIATION; PATHWAYS; CANCER; P53;

D O I：

10.1016/j.bbrc.2016.05.136

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The evidence suggests that transforming growth factor-beta (TGF-beta) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-beta 1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF-beta 1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-beta 1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (gamma H2AX). The levels of all three factors were similar right after irradiation regardless of TGF-beta 1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-beta 1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-beta type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF-beta 1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-beta 1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：420 / 425

页数：6

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