Biochemical and redox characterization of mitochondrial dual-specificity protein phosphatases 18 and 21 (DUSP18, DUSP21)

• Grant number: 25/13661-2
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Luciana Elena de Souza Fraga Machado
• Grantee: Luciana Elena de Souza Fraga Machado
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• Associated research grant: 19/02605-3 - Structural and functional characterization of mitochondrial protein phosphatases by redox metabolism and their role in cell biology, AP.JP
• Associated scholarship(s): 25/22879-1 - Biochemical and redox characterization of dual-specificity mitochondrial protein phosphatases 18 and 21 (DUSP18, DUSP21), BP.IC

Abstract

Dual-specificity protein phosphatases are atypical protein tyrosine phosphatases due to their ability to dephosphorylate tyrosine, serine and threonine residues, in addition to their smaller size. DUSPs 18 and 21 have an internal mitochondrial signal sequence anchored to the inner mitochondrial membrane faced to the intermembrane space and the mitochondrial matrix, respectively. While DUSP18 is expressed in all tissues, DUSP21 is specifically expressed in testes. The few studies with DUSP18 indicate that this enzyme is involved in the inactivation of the JNK kinase pathway in the cytoplasm and nucleus, through interaction with ataxin 1 and SAPK1. Although its functions in the cytoplasm and nucleus are controversial, this can be explained by its release into the cytoplasm after induction of apoptosis. However, the function of DUSP21 is still largely unknown. Additionally, although mitochondria are one of the main sources of oxidants, the redox regulation of these proteins is unexplored. Therefore, the main objective is to characterize these proteins biochemically for subsequent analysis with their substrates with the perspective of expanding the knowledge about their cellular functions. (AU)