DNA-PKcs-mediated stabilization of p53 by JNK2 is involved in arsenite-induced DNA damage and apoptosis in human embryo lung fibroblast cells

详细信息	查看全文 | 推荐本文 |

• 作者：Yuan Li^a ; ^b ; ¹ ; Yue Zhao^a ; ^b ; ¹ ; Rongrong Jiang^a ; ^b ; Yuan Xu^a ; ^b ; Min Ling^a ; ^b ; Ying Pang^a ; ^b ; Lu Shen^a ; ^b ; Yun Zhou^c ; Jianping Zhang^c ; Jianwei Zhou^b ; Xinru Wang^b ; Qizhan Liu^a ; ^b ; ^{drqzliu@hotmail.com}
• 关键词：DNA-PKcs ; dependent protein kinase catalytic subunit ; HELF ; human embryo lung fibroblast ; JNKs ; Jun-N-terminal kinases ; MAPKs ; mitogen activated protein kinases ; mdm2 ; murine double minute 2
• 刊名：Toxicology Letters
• 出版年：2012
• 期刊代码：49_03784274
• 类别：pha
• 出版时间：5 May, 2012
• 卷：210
• 期：3
• 页码：302-310
• 文件大小：1317 K

摘要

When cells encounter genotoxic stress, sensors for DNA lesions stabilize and activate p53; the signals involved, however, are largely unclear. Inorganic arsenite is a ubiquitous environmental contaminant associated with an increased risk of lung and skin damage and cancer. Although DNA double-strand breaks and apoptosis may relate to arsenite-induced damage and carcinogenesis, the mechanism of action remains obscure. Here, we find that, in human embryo lung fibroblast (HELF) cells, arsenite induces the activation of dependent protein kinase catalytic subunit (DNA-PKcs), which then phosphorylates and activates c-Jun N-terminal kinases 2 (JNK2), but not JNK1. As a positive regulator of p53, JNK2 binds to p53 and prevents p53 from murine double minute 2 (mdm2)-mediated, ubiquitin-proteasome-dependent degradation. Knockdown of DNA-PKcs/JNK2 signal pathway or p53 reduces apoptosis but elevates the DNA damage induced by a high level of arsenite. These results suggest that DNA-PKcs-mediated stabilization of p53 by JNK2 is involved in arsenite-induced DNA damage and apoptosis.