3 years ago

The CDK inhibitor p21 is a novel target gene of ATF4 and contributes to cell survival under ER stress

Shogo Ito, Shiori Kawachi, Yasumichi Inoue, Tsubasa Ohkubo, Daisuke Morishita, Nobumichi Ohoka, Yuka Itoh, Keishi Fukuura, Mai Nagasaka, Hidetoshi Hayashi
ATF4 is well-known for its role in the ER stress response. ATF4 also transcriptionally induces multiple effectors that determine cell fate depending on cellular context. In addition, ATF4 can communicate both pro-apoptotic and pro-survival signals. How ATF4 mediates its pro-survival roles, however, requires further investigation. Here, we report that the CDK inhibitor p21 is a novel target gene of ATF4. We identified two ATF4 responsive elements, one of which directly binds ATF4, within the first intron of the p21 gene. Importantly, overexpression of p21 enhances cell survival following ER stress induction, while p21 knockdown increases cell death. These results suggest that p21 induction plays a vital role in the cellular response to ER stress and indicate that p21 is a pro-survival effector of ATF4. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/1873-3468.12869

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