2. Academic Validation
  3. Oxidative stress reprograms the transcriptional coactivator Yki to suppress cell proliferation

Oxidative stress reprograms the transcriptional coactivator Yki to suppress cell proliferation

  • Cell Rep. 2024 Aug 27;43(8):114584. doi: 10.1016/j.celrep.2024.114584.
Xiaohan Sun 1,  Dafa Zhou 2,  Yuanfei Sun 2,  Yunhe Zhao 2,  Yanran Deng 3,  Xiaolin Pang 2,  Qingxin Liu 2,  Zizhang Zhou 4
Affiliations

Affiliations

  • 1 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.
  • 2 College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China.
  • 3 Key Laboratory of Biodiversity Conservation and Bioresource Utilization of Jiangxi Province, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China.
  • 4 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. Electronic address: zhouzz@jxnu.edu.cn.
PMID: 39106181 DOI: 10.1016/j.celrep.2024.114584
Abstract

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.

Keywords

CP: Cell biology; CP: Molecular biology; Foxo; Hippo pathway; Usp7; Yki; oxidative stress.

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