TAp73 contributes to the oxidative stress response by regulating protein synthesis

Proceedings of the National Academy of Sciences of the United States of America
Alberto MariniGerry Melino

Abstract

TAp73 is a transcription factor that plays key roles in brain development, aging, and cancer. At the cellular level, TAp73 is a critical homeostasis-maintaining factor, particularly following oxidative stress. Although major studies focused on TAp73 transcriptional activities have indicated a contribution of TAp73 to cellular metabolism, the mechanisms underlying its role in redox homeostasis have not been completely elucidated. Here we show that TAp73 contributes to the oxidative stress response by participating in the control of protein synthesis. Regulation of mRNA translation occupies a central position in cellular homeostasis during the stress response, often by reducing global rates of protein synthesis and promoting translation of specific mRNAs. TAp73 depletion results in aberrant ribosomal RNA (rRNA) processing and impaired protein synthesis. In particular, polysomal profiles show that TAp73 promotes the integration of mRNAs that encode rRNA-processing factors in polysomes, supporting their translation. Concurrently, TAp73 depletion causes increased sensitivity to oxidative stress that correlates with reduced ATP levels, hyperactivation of AMPK, and translational defects. TAp73 is important for maintaining active trans...Continue Reading

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Citations

Oct 21, 2018·Genes and Immunity·Giuseppe RaschellàAlessandra Gambacurta
Jun 20, 2019·PloS One·J Scott BeelerJennifer A Pietenpol
Jun 26, 2020·Cell Cycle·Niall BuckleyGerry Melino
Nov 30, 2018·Aging·Veronica CiuffoliEleonora Candi
Dec 12, 2018·Aging·Piervito LoprioreIvano Amelio
Nov 18, 2018·Aging·Artem SmirnovEleonora Candi
Dec 31, 2018·Aging·Valentina FrezzaFrancesca Bernassola
Apr 28, 2019·Journal of Cell Science·Ulrike TopfAgnieszka Chacinska
Feb 23, 2020·International Journal of Molecular Sciences·Chao WangKanaga Sabapathy
Dec 20, 2018·Genes and Immunity·Francesca PentimalliIvano Amelio
Apr 17, 2020·Disease Models & Mechanisms·John R P KnightAnne E Willis
Nov 18, 2020·Biochemistry. Biokhimii︠a︡·G Melino
Dec 11, 2020·Cell Death Discovery·Alessio ButeraGerry Melino
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Laura Maeso-AlonsoMaria C Marin
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Kyra LaubachXinbin Chen

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Methods Mentioned

BETA
flow cytometry
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