Characterization of the involvement of DUSP12 and its nuclear targets in the response of hepatic cell models to genotoxic stress

• Grant number: 22/13414-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Fábio Luis Forti
• Grantee: Viktor Kalbermatter Boell
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Protein tyrosine phosphatases (PTPs) catalyze the removal of phosphate groups from tyrosine residues in proteins and modulate the activity of their substrates. Approximately half of PTPs correspond to dual-specific protein tyrosine phosphatases (DUSPs), in which the catalytic activity also encompasses phosphoserine or phosphothreonine residues. In recent years, the involvement of DUSPs in several pathologies has been evidenced and further advances in the understanding of the biological activity of these phosphatases requires the identification of their substrates or acting partners. In this sense, it is worth noting the high expression of DUSP12 observed in cancer cells, which contributes to the acquisition of phenotypes favorable to tumor progression. Recently, our group identified the interaction of DUSP12 with nuclear proteins NAT10 and HP1BP3 in breast and lung adenocarcinoma cell lines subjected to different types of genotoxic stress, suggesting its involvement in gene expression regulation and genomic stability processes. However, investigations are needed to evaluate these interactions from a molecular and functional point of view in cells where the expression of these proteins is relevant to their phenotype. Thus, this project aims to characterize the response of hepatic cell lines under genotoxic stress conditions, investigating the involvement of DUSP12, NAT10 and HP1BP3 in mechanisms of maintenance of genomic stability. The results obtained by this project will certainly contribute to the understanding of the biological activity of DUSPs and will allow the proposition of new diagnostic and therapeutic strategies for patients with hepatocellular carcinoma and other hepatic pathologies.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERRUZO, PAULT Y. M.; BOELL, VIKTOR K.; RUSSO, LILIAN C.; OLIVEIRA, CARLA C.; FORTI, FABIO L.. DUSP3 modulates IRES-dependent translation of mRNAs through dephosphorylation of the HNRNPC protein in cells under genotoxic stimulus. BIOLOGY OF THE CELL, v. 116, n. 5, p. 15-pg., 2024-03-27. (20/00901-1, 22/04243-4, 15/03983-0, 18/01753-6, 22/13414-7)