Journal article

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

Kerrie-Ann Mcmahon, David A Stroud, Yann Gambin, Vikas Tillu, Michele Bastiani, Emma Sierecki, Mark E Polinkovsky, Thomas E Hall, Guillermo A Gomez, Yeping Wu, Marie-Odile Parat, Nick Martel, Harriet P Lo, Kum Kum Khanna, Kirill Alexandrov, Roger Daly, Alpha Yap, Michael T Ryan, Robert G Parton

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2021

Abstract

Caveolae-associated protein 3 (cavin3) 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. Cellular and cell-free expression assays revealed a direct interaction between BRCA1 and cavin3 that occurs when cavin3 is released from caveolae that are disassembled in response to UV and mechanical stress. Overexpression and RNAi-depletion revealed that cavin3 sensitized various cancer cells to UV-induced apoptosis. Supporting a role in DNA r..

View full abstract

University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

National Health and Medical Research Council APP1140064 Robert G Parton National Health and Medical Research Council APP1150083 Robert G Parton National Health and Medical Research Council APP1156489 Robert G Parton National Health and Medical Research Council APP1037320 Robert G Parton National Health and Medical Research Council APP1044041 Alpha Yap National Health and Medical Research Council APP1125390 Michael T Ryan National Health and Medical Research Council APP1070916 David A Stroud National Health and Medical Research Council APP1140851 David A Stroud The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.