Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response
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. 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..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 04. Nov. Zur Gesamtaufnahme - year:2022 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
McMahon, Kerrie-Ann [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| doi: |
10.1101/2020.07.26.222158 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI018424481 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI018424481 | ||
| 003 | DE-627 | ||
| 005 | 20230429081725.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200727s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.07.26.222158 |2 doi | |
| 035 | |a (DE-627)XBI018424481 | ||
| 035 | |a (biorXiv)10.1101/2020.07.26.222158 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a McMahon, Kerrie-Ann |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cavin3 released from caveolae interacts with BRCA1 to regulate the cellular stress response |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a 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. 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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Stroud, David A. |e verfasserin |4 aut | |
| 700 | 1 | |a Gambin, Yann |e verfasserin |4 aut | |
| 700 | 1 | |a Tillu, Vikas A. |e verfasserin |4 aut | |
| 700 | 1 | |a Bastiani, Michele |e verfasserin |4 aut | |
| 700 | 1 | |a Sierecki, Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Polinkovsky, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, Thomas E. |e verfasserin |4 aut | |
| 700 | 1 | |a Gomez, Guillermo A. |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yeping |e verfasserin |4 aut | |
| 700 | 1 | |a Parat, Marie-Odile |e verfasserin |4 aut | |
| 700 | 1 | |a Martel, Nick |e verfasserin |4 aut | |
| 700 | 1 | |a Lo, Harriet P. |e verfasserin |4 aut | |
| 700 | 1 | |a Khanna, Kum Kum |e verfasserin |4 aut | |
| 700 | 1 | |a Alexandrov, Kirill |e verfasserin |4 aut | |
| 700 | 1 | |a Daly, Roger |e verfasserin |4 aut | |
| 700 | 1 | |a Yap, Alpha S. |e verfasserin |4 aut | |
| 700 | 1 | |a Ryan, Michael T. |e verfasserin |4 aut | |
| 700 | 1 | |a Parton, Robert G. |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2022) vom: 04. Nov. |
| 773 | 1 | 8 | |g year:2022 |g day:04 |g month:11 |
| 856 | 4 | 0 | |u https://doi.org/10.7554/elife.61407 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.07.26.222158 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2022 |b 04 |c 11 | ||