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Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation

The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination and degradation in vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting in...

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Autores principales: Gao, Ming, Li, Xiaoguang, Dong, Wen, Jin, Rui, Ma, Hanghang, Yang, Pingxun, Hu, Meiru, Li, Yi, Hao, Yi, Yuan, Shengtao, Huang, Junjian, Song, Lun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664810/
https://www.ncbi.nlm.nih.gov/pubmed/23563151
http://dx.doi.org/10.1093/nar/gkt223
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author Gao, Ming
Li, Xiaoguang
Dong, Wen
Jin, Rui
Ma, Hanghang
Yang, Pingxun
Hu, Meiru
Li, Yi
Hao, Yi
Yuan, Shengtao
Huang, Junjian
Song, Lun
author_facet Gao, Ming
Li, Xiaoguang
Dong, Wen
Jin, Rui
Ma, Hanghang
Yang, Pingxun
Hu, Meiru
Li, Yi
Hao, Yi
Yuan, Shengtao
Huang, Junjian
Song, Lun
author_sort Gao, Ming
collection PubMed
description The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination and degradation in vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting in GADD45α accumulation to activate JNKs cell death pathway, thereby revealing a novel mechanism for the cellular GADD45α functional regulation. But the factors involved in GADD45α stability modulations are unidentified. Here, we demonstrated that MDM2 was an E3 ubiquitin ligase for GADD45α. One of MDM2-binding partner, ribosomal protein S7, interacted with and stabilized GADD45α through preventing the ubiquitination and degradation of GADD45α mediated by MDM2. This novel function of S7 is unrelated to p53 but seems to depend on S7/MDM2 interaction, for the S7 mutant lacking MDM2-binding ability lost its function to stabilize GADD45α. Further investigations indicated that arsenite treatment enhanced S7–MDM2 interaction, resulting in attenuation of MDM2-dependent GADD45α ubiquitination and degradation, thereby leading to GADD45α-dependent cell death pathway activation. Silencing S7 expression suppressed GADD45α-dependent cytotoxicity induced by arsenite. Our findings thus identify a novel function of S7 in control of GADD45α stabilization under both basal and stress conditions and its significance in mediating arsenite-induced cellular stress.
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spelling pubmed-36648102013-05-28 Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation Gao, Ming Li, Xiaoguang Dong, Wen Jin, Rui Ma, Hanghang Yang, Pingxun Hu, Meiru Li, Yi Hao, Yi Yuan, Shengtao Huang, Junjian Song, Lun Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination and degradation in vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting in GADD45α accumulation to activate JNKs cell death pathway, thereby revealing a novel mechanism for the cellular GADD45α functional regulation. But the factors involved in GADD45α stability modulations are unidentified. Here, we demonstrated that MDM2 was an E3 ubiquitin ligase for GADD45α. One of MDM2-binding partner, ribosomal protein S7, interacted with and stabilized GADD45α through preventing the ubiquitination and degradation of GADD45α mediated by MDM2. This novel function of S7 is unrelated to p53 but seems to depend on S7/MDM2 interaction, for the S7 mutant lacking MDM2-binding ability lost its function to stabilize GADD45α. Further investigations indicated that arsenite treatment enhanced S7–MDM2 interaction, resulting in attenuation of MDM2-dependent GADD45α ubiquitination and degradation, thereby leading to GADD45α-dependent cell death pathway activation. Silencing S7 expression suppressed GADD45α-dependent cytotoxicity induced by arsenite. Our findings thus identify a novel function of S7 in control of GADD45α stabilization under both basal and stress conditions and its significance in mediating arsenite-induced cellular stress. Oxford University Press 2013-05 2013-04-05 /pmc/articles/PMC3664810/ /pubmed/23563151 http://dx.doi.org/10.1093/nar/gkt223 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene Regulation, Chromatin and Epigenetics
Gao, Ming
Li, Xiaoguang
Dong, Wen
Jin, Rui
Ma, Hanghang
Yang, Pingxun
Hu, Meiru
Li, Yi
Hao, Yi
Yuan, Shengtao
Huang, Junjian
Song, Lun
Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation
title Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation
title_full Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation
title_fullStr Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation
title_full_unstemmed Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation
title_short Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation
title_sort ribosomal protein s7 regulates arsenite-induced gadd45α expression by attenuating mdm2-mediated gadd45α ubiquitination and degradation
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664810/
https://www.ncbi.nlm.nih.gov/pubmed/23563151
http://dx.doi.org/10.1093/nar/gkt223
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