跳转至内容
Merck
  • 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.

eLife (2021-06-19)
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
摘要

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.

材料
货号
品牌
产品描述

Sigma-Aldrich
Duolink®原位检测试剂(橙色)
Roche
抗-GFP, from mouse IgG1κ (clones 7.1 and 13.1)
Sigma-Aldrich
Duolink® 原位PLA® 抗兔MINUS探针
Sigma-Aldrich
Duolink® In Situ PLA® 探针抗小鼠PLUS
Sigma-Aldrich
抗肌动蛋白抗体,克隆C4, ascites fluid, clone C4, Chemicon®
Sigma-Aldrich
Anti-EGFR Antibody, clone LA22, clone LA22, Upstate®, from mouse
Sigma-Aldrich
抗-BRCA1抗体, serum, Upstate®
Sigma-Aldrich
Anti-ACLY antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-PTRF antibody produced in rabbit, IgG fraction of antiserum