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The CDK inhibitor p21 is a novel target gene of ATF 4 and contributes to cell survival under ER stress
Author(s) -
Inoue Yasumichi,
Kawachi Shiori,
Ohkubo Tsubasa,
Nagasaka Mai,
Ito Shogo,
Fukuura Keishi,
Itoh Yuka,
Ohoka Nobumichi,
Morishita Daisuke,
Hayashi Hidetoshi
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12869
Subject(s) - microbiology and biotechnology , unfolded protein response , endoplasmic reticulum , cdk inhibitor , transcription factor , effector , gene knockdown , activating transcription factor , biology , gene , protein kinase a , kinase , genetics , cyclin dependent kinase 2
Activating transcription factor 4 ( ATF 4) is well known for its role in the endoplasmic reticulum ( ER ) stress response. ATF 4 also transcriptionally induces multiple effectors that determine cell fate depending on cellular context. In addition, ATF 4 can communicate both pro‐apoptotic and pro‐survival signals. How ATF 4 mediates its prosurvival roles, however, requires further investigation. Here, we report that the CDK inhibitor p21 is a novel target gene of ATF 4. We identified two ATF 4‐responsive elements, one of which directly binds ATF 4, 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 prosurvival effector of ATF 4.