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Cavin3 released from caveolae interacts with BRCA1to regulate the cellular stress response
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.26.222158v1?rss=1
Authors: Parton, R. G., McMahon, K.-A., Stroud, D. A., Gambin, Y., Tillu, V., Bastiani, M., Sierecki, E., Polinkovsky, M., Hall, T. E., Gomez, G. A., Wu, Y., Parat, M.-O., Martel, N., Lo, H. P., Khanna, K. k., Alexandrov, K., Daly, R., Yap, A. S., Ryan, M.
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.
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.07.26.222158v1?rss=1
Authors: Parton, R. G., McMahon, K.-A., Stroud, D. A., Gambin, Y., Tillu, V., Bastiani, M., Sierecki, E., Polinkovsky, M., Hall, T. E., Gomez, G. A., Wu, Y., Parat, M.-O., Martel, N., Lo, H. P., Khanna, K. k., Alexandrov, K., Daly, R., Yap, A. S., Ryan, M.
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.
Copy rights belong to original authors. Visit the link for more info