| Grant number: | 20/08684-0 |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| Start date: | January 01, 2021 |
| End date: | December 31, 2025 |
| Field of knowledge: | Health Sciences - Nutrition - Nutrition Biochemistry |
| Principal Investigator: | Fernando Moreira Simabuco |
| Grantee: | Mariana Marcela Góis |
| Host Institution: | Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil |
| Associated research grant: | 18/14818-9 - Study of molecular targets important for the control of cancer metabolism - the mTOR/S6K pathway as a central role, AP.JP2 |
| Associated scholarship(s): | 23/02842-0 - Assessing the role of S6K1 and S6K2 in DNA damage response and repair, BE.EP.DD |
Abstract PARP-1 is a protein involved in DNA repair, DNA replication, transcription, genome organization and apoptosis. Once activated by DNA damage, PARP proteins are able to post-translation- modify proteins in a process called parylation, using NAD+ as substrate. Several studies have proved the feasibility of the use of PARP inhibitors as adjuvant chemotherapeutic agents for the treatment of cancer or as a monotherapy against tumor cells that are defective in DNA repair mechanisms, like in BRCA-deficient cancer cells. In an article published by our group we have shown that PARP-1 efficiently co-immunoprecipitates with S6K2 and other studies have also demonstrated correlation between PARP-1 and the mTOR/S6Ks pathway. Here we aim to further explore the relationship between PARP-1 and S6Ks, since we still don't know if S6Ks regulate or are regulated by PARP1. By performing immunoprecipitation experiments we intend to characterize the interaction between PARP-1 and S6K2. Besides, we will evaluate whether PARP-1 is able to parylate S6Ks or S6Ks are able to phosphorylate PARP-1 and how this alters the functions of the proteins. Finally, the relationship between PARP-1 and mTOR/S6Ks will be explored in the cancer context, using a breast cancer model and inhibitors of PARP-1. This project may contribute for the understanding on how cancer cells regulate metabolism in the presence of DNA damage or how nutrient availability connects to DNA repair machinery. | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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