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Updated: Nov 1, 2025

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
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Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

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Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response

Kerrie-Ann McMahon1, David A Stroud2, Yann Gambin1

  • 1Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia.

Elife
|June 18, 2021
PubMed

Insights

Caveolae-associated protein 3 (cavin3) plays a crucial role in DNA repair and cancer cell apoptosis. Loss of cavin3 impairs DNA repair and reduces cancer cell sensitivity to UV-induced apoptosis and PARP inhibition.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Caveolae-associated protein 3 (cavin3) is frequently inactivated in various cancers.
  • Understanding cavin3's role in cellular processes is critical for cancer therapy.

Purpose of the Study:

  • To elucidate the function of cavin3 in the cellular proteome, focusing on its role in DNA repair and cancer cell survival.
  • To investigate the interaction between cavin3 and BRCA1 in response to cellular stress.

Main Methods:

  • Genome-edited cells and label-free quantitative proteomics were employed to analyze the cellular proteome.
  • Cellular and cell-free expression assays were used to determine direct interactions between proteins.
  • Overexpression and RNAi-depletion studies assessed the impact of cavin3 on UV-induced apoptosis and PARP inhibition sensitivity.

Main Results:

  • Cavin3 deletion led to downregulation of BRCA1 and BRCA1 A-complex components, indicating a role in DNA repair.
  • A direct interaction between cavin3 and BRCA1 was identified, occurring upon caveolae disassembly induced by UV and mechanical stress.
  • Cavin3 overexpression sensitized cancer cells to UV-induced apoptosis, while cavin3 deficiency increased sensitivity to PARP inhibition, which was modulated by 53BP1.

Conclusions:

  • Cavin3 collaborates with BRCA1 in critical cancer-related pathways, including DNA repair and apoptosis regulation.
  • Loss of cavin3 function may promote tumor cell survival by reducing apoptotic sensitivity and impairing DNA repair under stress.
  • Cavin3 represents a potential therapeutic target for enhancing cancer treatment efficacy.
Keywords:
BRCA1breast cancercancer biologycaveolaecavin proteinscell biology

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