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Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)

Resveratrol possesses a strong anticancer activity exhibited as the induction of apoptosis through p53 activation. However, the molecular mechanism and direct target(s) of resveratrol-induced p53 activation remain elusive. Here, the Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)...

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Autores principales: Oi, Naomi, Yuan, Jian, Malakhova, Margarita, Luo, Kuntian, Li, Yunhui, Ryu, Joohyun, Zhang, Lei, Bode, Ann M., Xu, Zengguang, Li, Yan, Lou, Zhenkun, Dong, Zigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286533/
https://www.ncbi.nlm.nih.gov/pubmed/24998844
http://dx.doi.org/10.1038/onc.2014.194
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author Oi, Naomi
Yuan, Jian
Malakhova, Margarita
Luo, Kuntian
Li, Yunhui
Ryu, Joohyun
Zhang, Lei
Bode, Ann M.
Xu, Zengguang
Li, Yan
Lou, Zhenkun
Dong, Zigang
author_facet Oi, Naomi
Yuan, Jian
Malakhova, Margarita
Luo, Kuntian
Li, Yunhui
Ryu, Joohyun
Zhang, Lei
Bode, Ann M.
Xu, Zengguang
Li, Yan
Lou, Zhenkun
Dong, Zigang
author_sort Oi, Naomi
collection PubMed
description Resveratrol possesses a strong anticancer activity exhibited as the induction of apoptosis through p53 activation. However, the molecular mechanism and direct target(s) of resveratrol-induced p53 activation remain elusive. Here, the Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1) was identified as a potential target of resveratrol, and in vitro binding assay results using resveratrol (RSVL)-conjugated Sepharose 4B beads confirmed their direct binding. Depletion of G3BP1 significantly diminishes resveratrol-induced p53 expression and apoptosis. We also found that G3BP1 negatively regulates p53 expression by interacting with ubiquitin-specific protease 10 (USP10), a deubiquitinating enzyme of p53. Disruption of the interaction of p53 with USP10 by G3BP1 interference leads to suppression of p53 deubiquitination. Resveratrol, on the other hand, directly binds to G3BP1 and prevents the G3BP1/USP10 interaction, resulting in enhanced USP10-mediated deubiquitination of p53 and consequently increased p53 expression. These findings disclose a novel mechanism of resveratrol-induced p53 activation and resveratrol-induced apoptosis by direct targeting of G3BP1.
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spelling pubmed-42865332015-11-14 Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1) Oi, Naomi Yuan, Jian Malakhova, Margarita Luo, Kuntian Li, Yunhui Ryu, Joohyun Zhang, Lei Bode, Ann M. Xu, Zengguang Li, Yan Lou, Zhenkun Dong, Zigang Oncogene Article Resveratrol possesses a strong anticancer activity exhibited as the induction of apoptosis through p53 activation. However, the molecular mechanism and direct target(s) of resveratrol-induced p53 activation remain elusive. Here, the Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1) was identified as a potential target of resveratrol, and in vitro binding assay results using resveratrol (RSVL)-conjugated Sepharose 4B beads confirmed their direct binding. Depletion of G3BP1 significantly diminishes resveratrol-induced p53 expression and apoptosis. We also found that G3BP1 negatively regulates p53 expression by interacting with ubiquitin-specific protease 10 (USP10), a deubiquitinating enzyme of p53. Disruption of the interaction of p53 with USP10 by G3BP1 interference leads to suppression of p53 deubiquitination. Resveratrol, on the other hand, directly binds to G3BP1 and prevents the G3BP1/USP10 interaction, resulting in enhanced USP10-mediated deubiquitination of p53 and consequently increased p53 expression. These findings disclose a novel mechanism of resveratrol-induced p53 activation and resveratrol-induced apoptosis by direct targeting of G3BP1. 2014-07-07 2015-05-14 /pmc/articles/PMC4286533/ /pubmed/24998844 http://dx.doi.org/10.1038/onc.2014.194 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Oi, Naomi
Yuan, Jian
Malakhova, Margarita
Luo, Kuntian
Li, Yunhui
Ryu, Joohyun
Zhang, Lei
Bode, Ann M.
Xu, Zengguang
Li, Yan
Lou, Zhenkun
Dong, Zigang
Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)
title Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)
title_full Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)
title_fullStr Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)
title_full_unstemmed Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)
title_short Resveratrol induces apoptosis by directly targeting Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP1)
title_sort resveratrol induces apoptosis by directly targeting ras-gtpase activating protein sh3 domain binding protein 1 (g3bp1)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286533/
https://www.ncbi.nlm.nih.gov/pubmed/24998844
http://dx.doi.org/10.1038/onc.2014.194
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