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Heterogeneous ribonucleoprotein K role in DNA repair in oral epidermoid cells

Grant number: 19/16914-8
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2019
Effective date (End): October 31, 2021
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Andréia Machado Leopoldino
Grantee:Ana Júlia Rossoni Carvalho
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Heterogeneous ribonucleoprotein K (hnRNPK) has been described as increased in many cancers, including in oral cancer, and associated with their worse prognosis. This protein binds toRNA and DNA and participates in different regulatory protein-protein interactions, being found in the nucleus, cytosol and mitochondria. HnRNPK protein is the target of a series of post-translational modifications, such as methylation and phosphorylation, which in turn regulates its different interactions to other proteins and its subcellular location, ensuring that it is associated with different mechanisms of gene regulation, like transcription, RNA processing, translation and messenger RNA stability. HnRNPK has ample interaction with mitochondrial proteins, integrating signals from different signaling pathways in the nucleus, cytoplasm and mitochondria. Considering: i) its relation to cancer; ii) the occurrence of mitochondrial DNA damage; iii) the DNA repair mechanisms present in this organelle; iv) previous data from out group demonstrating the interaction between YB-1 and hnRNPK; and v) the need of YB-1 for mismatch repair, our hypothesis is that hnRNPK acts in the DNA repairsystem both in nucleus and mitochondria. Thus, our objective is to characterize the potentialinvolvement of hnRNPK in DNA repair through its interaction with YB-1, focusing in the mismatchrepair and excision repair systems. Molecular biology, biochemistry and molecular genetics strategieswill be used, as well as in vitro assays of protein/protein/DNA interaction and functional assays usinghuman cell lines of oral epidermoid cells (tumoral and non-tumoral) with altered levels of hnRNPKand/or inhibitors of signaling pathways of hnRNPK regulation. We expect the results to contribute toa better understanding of the role of hnRNPK in the development and progression of different typesof cancer, such as oral cancer. (AU)