Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response
Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response
Abstract Caveolae-associated protein 3 (cavin3), a putative tumor suppressor protein, is inactivated in most cancers. We characterized how cavin3 affects the cellular proteome using genome-edited cells together with label-free quantitative proteomics. These studies revealed a prominent role for cavin3 in DNA repair with BRCA1 and BRCA1 A-complex components being downregulated on cavin3 deletion. Using cellular and cell-free expression assays, we show a direct interaction between BRCA1 and cavin3. Association of BRCA1 and cavin3 occurs when cavin3 is released from caveolae that are disassembled in response to UV and mechanical stress. Supporting a role in DNA repair, cavin3-deficient cells were sensitized to the effects of PARP inhibition, which compromises DNA repair, and showed reduced recruitment of the BRCA1 A-complex to UV DNA damage foci. Overexpression and RNAi-depletion revealed that cavin3 sensitized various cancer cells to UV-induced apoptosis. We conclude that cavin3 functions together with BRCA1 in multiple pathways that contribute to tumorigenesis.
Bastiani Michele、Stroud David A.、Gomez Guillermo A.、Lo Harriet P.、Khanna Kum Kum、Polinkovsky Mark、Ryan Michael T.、Parton Robert G.、Hall Thomas E.、Gambin Yann、McMahon Kerrie-Ann、Wu Yeping、Martel Nick、Daly Roger、Sierecki Emma、Alexandrov Kirill、Yap Alpha S.、Parat Marie-Odile、Tillu Vikas A.
The University of Queensland, Institute for Molecular Bioscience, University of QueenslandDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of MelbourneThe University of Queensland, Institute for Molecular Bioscience, University of Queensland||Centre for Cancer Biology, South Australia Pathology and the University of South AustraliaThe University of Queensland, Institute for Molecular Bioscience, University of QueenslandSignal Transduction Laboratory, QIMR Berghofer Medical Research InstituteThe University of Queensland, Institute for Molecular Bioscience, University of Queensland||Acrondis AGMonash Biomedicine Discovery Institute, Department of Biochemistry & Molecular Biology, Monash UniversityThe University of Queensland, Institute for Molecular Bioscience, University of Queensland||The University of Queensland, Centre for Microscopy and Microanalysis, University of QueenslandThe University of Queensland, Institute for Molecular Bioscience, University of QueenslandThe University of Queensland, Institute for Molecular Bioscience, University of Queensland||EMBL Australia Node in Single Molecule Science, Lowy Cancer building, Level 3 Medical Sciences UNSW Kensington CampusThe University of Queensland, Institute for Molecular Bioscience, University of QueenslandThe University of Queensland, Institute for Molecular Bioscience, University of QueenslandThe University of Queensland, Institute for Molecular Bioscience, University of QueenslandMonash Biomedicine Discovery Institute, Department of Biochemistry & Molecular Biology, Monash UniversityThe University of Queensland, Institute for Molecular Bioscience, University of Queensland||EMBL Australia Node in Single Molecule Science, Lowy Cancer building, Level 3 Medical Sciences UNSW Kensington CampusThe University of Queensland, Institute for Molecular Bioscience, University of Queensland||CSIRO-QUT Synthetic Biology Alliance, ARC Centre of Excellence in Synthetic BiologyThe University of Queensland, Institute for Molecular Bioscience, University of QueenslandThe University of Queensland, School of PharmacyThe University of Queensland, Institute for Molecular Bioscience, University of Queensland
基础医学分子生物学肿瘤学
BRCA1breast cancercaveolaecavin proteins
Bastiani Michele,Stroud David A.,Gomez Guillermo A.,Lo Harriet P.,Khanna Kum Kum,Polinkovsky Mark,Ryan Michael T.,Parton Robert G.,Hall Thomas E.,Gambin Yann,McMahon Kerrie-Ann,Wu Yeping,Martel Nick,Daly Roger,Sierecki Emma,Alexandrov Kirill,Yap Alpha S.,Parat Marie-Odile,Tillu Vikas A..Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.07.26.222158.点此复制
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