UV Radiation-induced Impairment of Cellular Morphology and Motility is Enhanced by DUSP3/VHR Loss and FAK Activation

Autor(es)

Pereira, Nadine Ranieri ^[1] ; Russo, Lilian Cristina ^[1] ; Forti, Fabio Luis ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Lab Biomol Syst Signalling, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cell Biochemistry and Biophysics; v. 79, n. 2 JAN 2021.
• Citações Web of Science: 1

Resumo

DUSP3 is a phosphatase expressed and active in several tissues that dephosphorylates tyrosine residues in many regulatory proteins of cellular activities such as proliferation, survival, and cell death. Recently, two new independent functions were assigned to this enzyme: dephosphorylation of focal adhesion kinase (FAK) and regulation of nucleotide-excision repair (NER) pathway. Genotoxic stress by UV radiation is known to affect cell morphology, adhesion, and migration for affecting, for example, the Rho GTPases that regulate actin cytoskeleton. This work investigated the intersection of DUSP3 function, XPA protein activity, and UV toxicity by examining cell migration, FAK, and SRC kinase phosphorylation status, in addition to cell morphology, in fibroblast cells proficient (MRC-5) or deficient (XPA) of the NER pathway. DUSP3 loss reduced cell migration of normal cells, which was stimulated by the genotoxic stress, effects evidenced in presence of serum mitogenic stimulus. However, NER-deficient cells migration response was the opposite since DUSP3 loss increased migration, especially after cells being exposed to UV stress. The levels of pFAK(Y397) peaked 15 min and 1 h after UV radiation in normal cells, but only slightly increased in repair-deficient cells. However, the DUSP3 knockdown strongly raised pFAK(Y397) levels in both cells, but especially in XPA cells as supported by the higher SRC activity. These effects impacted on the dynamics of actin-based structures formation, such as stress fibres, apparently dependent on DUSP3 and DNA-repair (NER) proficiency of the cells. Altogether our findings suggest this dual-phosphatase is bridging gaps between the complex regulation of cell morphology, motility, and genomic stability. (AU)

• Processo FAPESP: 15/03983-0 - Investigação molecular e funcional da interação de DUSP3 com proteínas nucleares: implicações em mecanismos de reparo de DNA
• Beneficiário: Fábio Luis Forti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/01753-6 - Identificação e investigação funcional de proteínas que interagem com as enzimas Cdc42 e DUSP12 em células humanas sob condições de instabilidade genômica: uma abordagem proteômica
• Beneficiário: Fábio Luis Forti
• Modalidade de apoio: Auxílio à Pesquisa - Regular