Functional and molecular evaluation of DUSP12 phosphatase in human tumor cells subjected to stress conditions

• Grant number: 22/04243-4
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2022
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Fábio Luis Forti
• Grantee: Fábio Luis Forti
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Roberto Kopke Salinas ; William Tadeu Lara Festuccia
• Associated scholarship(s): 23/02380-7 - Cloning of human HP1BP3 and NAT10 genes in prokaryotic and eukaryotic expression vectors, BP.TT

Abstract

A better understanding on the mechanisms of action of tyrosine phosphatase DUSP12 can identify potential correlations with cellular disorders and suggest strategies of intervention on its enzymatic activity, unveiling it as a drug target of clinical interest. This dual-specificity tyrosine phosphatase (DUSP) is known to preferentially dephosphorylate phospho-tyrosine - but also phospho-serine or phospho-threonine - on protein substrates. It is largely expressed in several types of normal tissues and human tumors such as breast, cervix, colon, lung, pancreas, liver, stomach, and blood. There is experimental evidence that this enzyme can mediate, direct or indirectly, regulatory mechanisms of genomic stability maintenance such as cell cycle, DNA repair, chromatin organization, gene expression and even nuclear architecture, which are essential for processes of transformation and/or resistance tumor. Our group identified nuclear protein partners of DUSP12 in breast and lung adenocarcinoma cell lines subjected to different types of genotoxic stress and found important functional connections with the cytoskeleton, chromatin, splicing machinery and ribosomal maturation. This project aims to investigate molecular and functional details of the DUSP12 protein and its interaction with the HP1BP3 and NAT10 proteins. The understanding of the functional relationships between them and the mechanisms of chromatin integrity and organization may point to the unexplored relevance of this phosphatase for nuclear processes involved with the malignancy of certain tumor cells. (AU)

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)