Characterization of PIMREG in DNA damage signaling pathways induced by ionizing radiation in GBM cells

• Grant number: 22/13336-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Leticia Fröhlich Archangelo
• Grantee: Laís do Carmo
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

PIMREG (PICALM interacting mitotic regulator) is a nuclear protein enriched in the nucleolus and highly expressed in the thymus and in the spleen. Besides that, it is a substrate of the anaphase/cyclosome promoter complex (APC/C), playing a role as a mitotic regulator. Also, PIMREG function is related to carcinogenesis, since its expression is increased in several types of cancer, especially in glioblastoma (GBM) - where its high expression is related to poor patient survival and tumor progression. Recent data from our group showed that PIMREG is related to DNA damage pathways since its protein levels increase in GBM cells that accumulated DNA damage upon genotoxic insults, such as exposure to chemotherapeutic drugs (temozolomide, hydroxyurea and cisplatin) and ionizing radiation (IR). Furthermore, knockdown of PIMREG interfered with the ATM and ATR kinase pathways and increased the sensitivity of the cells to TMZ treatment. Thus, this project aims to investigate the participation and positioning of PIMREG in DNA damage signaling pathways, specifically those induced by IR, since radiotherapy is one of the main treatments for GBM and induces the main signaling pathways to DNA double-strand break damage - Homologous Recombination and Non-Homologous End Joining. To this end, parental T98G GBM cells, with deletion (T89G cells knockout PIMREG-/-), and with overexpression of PIMREG, will be subjected to IR and Western Blot analysis. So that the expression and activation of DNA damage proteins could be analyzed as well as the possible interference that PIMREG exhibits in these pathways.