Oxidative stress reprograms the transcriptional coactivator Yki to suppress cell proliferation

Area of Science:

• Cell biology
• Molecular biology
• Genetics

Background:

• The transcriptional coactivator Yorkie (Yki) is a key regulator of organ size by promoting cell proliferation.
• The precise mechanisms controlling Yki activity under cellular stress, such as oxidative stress, remain largely unknown.

Purpose of the Study:

• To elucidate how cells regulate Yorkie (Yki) activity in response to oxidative stress.
• To identify the molecular players and mechanisms involved in Yki-mediated cellular responses to oxidative stress.

Main Methods:

• Investigated protein-protein interactions between Yki, Scalloped (Sd), and forkhead box O (Foxo) under oxidative stress conditions.
• Utilized molecular biology techniques to analyze gene expression changes related to proliferation and stress response.
• Assessed the role of Usp7 in the deubiquitination of Foxo and its subsequent interaction with Yki.
• Evaluated the necessity of Yki for survival in Drosophila models exposed to oxidative stress.

Main Results:

• Oxidative stress disrupts the Yki-Scalloped (Sd) complex formation.
• Oxidative stress promotes the interaction between Yki and forkhead box O (Foxo).
• Usp7 deubiquitinates Foxo, enhancing its binding affinity to Yki and activating proliferation suppressor genes.
• Yki is indispensable for Drosophila survival during oxidative stress.

Conclusions:

• Oxidative stress triggers a reprogramming of Yki function, shifting it from a proliferation promoter to a proliferation suppressor.
• This Yki-mediated reprogramming constitutes a critical self-protective mechanism against oxidative damage.
• The findings reveal a novel pathway for cellular adaptation to harmful stimuli involving transcription factor dynamics.