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

Area of Science:

• Molecular Biology
• Biochemistry
• Cancer Research

Background:

• Resveratrol exhibits anticancer properties by inducing apoptosis via p53 activation.
• The precise molecular targets and mechanisms of resveratrol-induced p53 activation are not fully understood.

Purpose of the Study:

• To identify the direct molecular target of resveratrol responsible for p53 activation.
• To elucidate the mechanism by which resveratrol influences p53 expression and subsequent apoptosis.

Main Methods:

• In vitro binding assays using resveratrol-conjugated Sepharose 4B beads to identify direct binding partners.
• G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein 1) depletion studies to assess its role in resveratrol's effects.
• Investigation of the interaction between G3BP1, USP10 (ubiquitin-specific protease 10), and p53.

Main Results:

• G3BP1 was identified as a direct binding target of resveratrol.
• Depletion of G3BP1 significantly reduced resveratrol-induced p53 expression and apoptosis.
• G3BP1 negatively regulates p53 by interacting with USP10, inhibiting p53 deubiquitination. Resveratrol disrupts this interaction, enhancing p53 deubiquitination and expression.

Conclusions:

• Resveratrol directly targets G3BP1, uncovering a novel mechanism for p53 activation.
• This G3BP1-mediated pathway is crucial for resveratrol-induced apoptosis, offering new therapeutic insights.