Investigation of VHR (DUSP3) protein tyrosine phosphatase in DNA damage response induced by ultraviolet light in human melanoma cell lines

• Grant number: 11/05822-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2011
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Fábio Luis Forti
• Grantee: Alexsandro dos Santos
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The dual-specificity protein tyrosine phosphatases (DUSP) are members of the larger family of protein tyrosine phosphatases (PTPs) and have been implicated as central regulators of mitogenic and other signaling pathways mediated by the families of mitogen-activated protein kinases (MAPK). One of these MAPK phosphatases (MKPs) is the 185-amino acid long VHR, which was cloned based on its homology with the first identified dual-specific phosphatase, the Vaccinia virus H1 open reading-frame. VHR is a small dual-specific phosphatase with specificity for the MAPKs Erk2 and Jnk, being an important molecule for cell cycle progression. Recent studies have shown important roles for serine/threonine protein phosphatases in DNA damage responses. There are studies pointing to a role of PP2A in up- or downregulate important proteins such as ATM, CHK1, p53 and pH2AX. However, it is practically inexistent data about protein tyrosine phosphatases regulating nuclear activities as chromatin remodeling, mitosis and DNA damage/repair. The aim of this study is to investigate the involvement of VHR (DUSP3) and its function on DNA damage/repair response in human melanoma cell lines exposed to ultraviolet light. Moreover, we will study the interactions of VHR with another classical proteins related to DNA repair pathways and construct or predict novel protein-protein networks in human melanoma cell lines. (AU)

Scientific publications

(7)

(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)

ESPINHA, GISELE; OSAKI, JULIANA HARUMI; COSTA, ERICO TOSONI; FORTI, FABIO LUIS. Inhibition of the RhoA GTPase Activity Increases Sensitivity of Melanoma Cells to UV Radiation Effects. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2016. (15/03983-0, 10/09453-0, 11/05822-3)

TORRES, THOMPSON E. P.; RUSSO, LILIAN C.; SANTOS, ALEXSANDRO; MARQUES, GABRIELA R.; MAGALHAES, YULI T.; TABASSUM, SARTAJ; FORTI, FABIO L.. Loss of DUSP3 activity radiosensitizes human tumor cell lines via attenuation of DNA repair pathways. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 7, p. 1879-1894, JUL 2017. (15/03983-0, 11/05822-3)

ESPINHA, GISELE; OSAKI, JULIANA H.; MAGALHAES, YULI T.; FORTI, FABIO LUIS. Rac1 GTPase-deficient HeLa cells present reduced DNA repair, proliferation, and survival under UV or gamma irradiation. Molecular and Cellular Biochemistry, v. 404, n. 1-2, p. 281-297, JUN 2015. (11/05822-3)

MAGALHAES, YULI T.; SILVA, GISELE E. T.; OSAKI, JULIANA H.; ROCHA, CLARISSA R. R.; FORTI, FABIO L.. RHOAming Through the Nucleotide Excision Repair Pathway as a Mechanism of Cellular Response Against the Effects of UV Radiation. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 8, AUG 19 2020. (11/05822-3, 10/09453-0, 18/01753-6, 15/03983-0, 10/20506-8, 17/01451-7)

OSAKI, JULIANA H.; ESPINHA, GISELE; MAGALHAES, YULI T.; FORTI, FABIO L.. Modulation of RhoA GTPase Activity Sensitizes Human Cervix Carcinoma Cells to gamma-Radiation by Attenuating DNA Repair Pathways. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2016, p. 11-pg., 2016-01-01. (11/05822-3, 15/18341-4)

OSAKI, JULIANA H.; ESPINHA, GISELE; MAGALHAES, YULI T.; FORTI, FABIO L.. Modulation of RhoA GTPase Activity Sensitizes Human Cervix Carcinoma Cells to gamma-Radiation by Attenuating DNA Repair Pathways. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2016. (11/05822-3, 15/18341-4)

ESPINHA, GISELE; OSAKI, JULIANA HARUMI; COSTA, ERICO TOSONI; FORTI, FABIO LUIS. Inhibition of the RhoA GTPase Activity Increases Sensitivity of Melanoma Cells to UV Radiation Effects. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2016, p. 14-pg., 2016-01-01. (11/05822-3, 10/09453-0, 15/03983-0)