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

• DOI: 10.7554/elife.61407
• Publication Date: 2021-06-18T12:00:25Z
• Authors: 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
• Keywords: Cellular stress response; Proteome

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 DNA repair, BRCA1 and A-complex components being downregulated on deletion. Cellular cell-free expression assays direct interaction between that occurs when released from caveolae are disassembled response to UV mechanical stress. Overexpression RNAi-depletion sensitized various cancer UV-induced apoptosis. Supporting cavin3-deficient were sensitive PARP inhibition, where concomitant depletion of 53BP1 restored BRCA1-dependent sensitivity inhibition. conclude functions multiple cancer-related pathways. The loss function may provide tumor cell survival by attenuating apoptotic hindering repair under chronic stress conditions.