Projects per year
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 repair, cavin3-deficient cells were sensitive to PARP inhibition, where concomitant depletion of 53BP1 restored BRCA1-dependent sensitivity to PARP inhibition. We conclude that cavin3 functions together with BRCA1 in multiple cancer-related pathways. The loss of cavin3 function may provide tumor cell survival by attenuating apoptotic sensitivity and hindering DNA repair under chronic stress conditions.
Original language | English |
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Article number | e61407 |
Number of pages | 35 |
Journal | eLife |
Volume | 10 |
DOIs | |
Publication status | Published - Jun 2021 |
Keywords
- BRCA1
- Breast cancer
- Caveolae
- Cavin proteins
Projects
- 4 Finished
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Translating membrane proteins into therapeutics; from bedside to bench
Sexton, P., Christopoulos, A., Pantelis, C. & Parton, R. G.
1/01/19 → 31/12/23
Project: Research
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Systems approaches to understanding mitochondrial function and dysfunction in disease
Stroud, D.
1/01/18 → 31/12/21
Project: Research
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Assembly and misassembly of mitochondrial respiratory chain Complex I
Ryan, M., Stroud, D. & Thorburn, D. R.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/17 → 31/12/19
Project: Research