Revisiting the roles of VHR/DUSP3 phosphatase in human diseases

Authors

  • Lilian Cristina Russo Universidade de Sao Paulo. Instituto de Quimica. Departamento de Bioquímica
  • Jéssica Oliveira Farias Universidade de Sao Paulo. Instituto de Quimica. Departamento de Bioquímica
  • Pault Yeison Minaya Ferruzo Universidade de Sao Paulo. Instituto de Quimica. Departamento de Bioquímica
  • Lucas Falcão Monteiro Universidade de Sao Paulo. Instituto de Quimica. Departamento de Bioquímica
  • Fábio Luís Forti Universidade de São Paulo. Instituto de Quimíca. Departamento de Bioquímica

DOI:

https://doi.org/10.6061/clinics/2018/e466s

Keywords:

Protein tyrosine phosphatase (PTP), Vaccinia H1-related phosphatase (VHR), Dual-specificity phosphatase 3 (DUSP3), Mitogen-activated protein kinase (MAPK)

Abstract

Protein tyrosine phosphatases have long been considered key regulators of biological processes and are therefore implicated in the origins of various human diseases. Heterozygosity, mutations, deletions, and the complete loss of some of these enzymes have been reported to cause neurodegenerative diseases, autoimmune syndromes, genetic disorders, metabolic diseases, cancers, and many other physiological imbalances. Vaccinia H1-related phosphatase, also known as dual-specificity phosphatase 3, is a protein tyrosine phosphatase enzyme that regulates the phosphorylation of the mitogen-activated protein kinase signaling pathway, a central mediator of a diversity of biological responses. It has been suggested that vaccinia H1-related phosphatase can act as a tumor suppressor or tumor-promoting phosphatase in different cancers. Furthermore, emerging evidence suggests that this enzyme has many other biological functions, such as roles in immune responses, thrombosis, hemostasis, angiogenesis, and genomic stability, and this broad spectrum of vaccinia H1-related phosphatase activity is likely the result of its diversity of substrates. Hence, fully identifying and characterizing these substrate-phosphatase interactions will facilitate the identification of pharmacological inhibitors of vaccinia H1-related phosphatase that can be evaluated in clinical trials. In this review, we describe the biological processes mediated by vaccinia H1-related phosphatase, especially those related to genomic stability. We also focus on validated substrates and signaling circuitry with clinical relevance in human diseases, particularly oncogenesis.

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Published

2019-02-14

Issue

Section

Review Articles

How to Cite

Russo, L. C., Farias, J. O., Ferruzo, P. Y. M., Monteiro, L. F., & Forti, F. L. (2019). Revisiting the roles of VHR/DUSP3 phosphatase in human diseases. Clinics, 73(Suppl. 1), e466s. https://doi.org/10.6061/clinics/2018/e466s