Oxidative stress reprograms the transcriptional coactivator Yki to suppress cell proliferation
Xiaohan Sun,
Dafa Zhou,
Yuanfei Sun,
Yunhe Zhao,
Yanran Deng,
Xiaolin Pang,
Qingxin Liu,
Zizhang Zhou
Affiliations
Xiaohan Sun
Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China; School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255000, China
Dafa Zhou
College of Life Sciences, Shandong Agricultural University, Tai’an 271018, China
Yuanfei Sun
College of Life Sciences, Shandong Agricultural University, Tai’an 271018, China
Yunhe Zhao
College of Life Sciences, Shandong Agricultural University, Tai’an 271018, China
Yanran Deng
Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China
Xiaolin Pang
College of Life Sciences, Shandong Agricultural University, Tai’an 271018, China
Qingxin Liu
College of Life Sciences, Shandong Agricultural University, Tai’an 271018, China
Zizhang Zhou
Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China; College of Life Sciences, Shandong Agricultural University, Tai’an 271018, China; Corresponding author
Summary: The transcriptional coactivator Yorkie (Yki) regulates organ size by promoting cell proliferation. It is unclear how cells control Yki activity when exposed to harmful stimuli such as oxidative stress. In this study, we show that oxidative stress inhibits the binding of Yki to Scalloped (Sd) but promotes the interaction of Yki with another transcription factor, forkhead box O (Foxo), ultimately leading to a halt in cell proliferation. Mechanistically, Foxo normally exhibits a low binding affinity for Yki, allowing Yki to form a complex with Sd and activate proliferative genes. Under oxidative stress, Usp7 deubiquitinates Foxo to promote its interaction with Yki, thereby activating the expression of proliferation suppressors. Finally, we show that Yki is essential for Drosophila survival under oxidative stress. In summary, these findings suggest that oxidative stress reprograms Yki from a proliferation-promoting factor to a proliferation suppressor, forming a self-protective mechanism.
