Dual-specificity protein phosphatase 1: A potential therapeutic target in cancer
Suryakant Niture, Blaine H. M. Mooers, Dee Wu, Matthew Hart, Jerry J. Jaboin, Danushka S. Seneviratne
Abstract
Dual-specificity protein phosphatase 1 (DUSP1), also known as MAP kinase phosphatase 1 (MKP1), is a key member of the dual-specificity phosphatase family that dephosphorylates both threonine and tyrosine residues on mitogen-activated protein kinases (MAPKs). By inactivating critical MAPK signaling pathways, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, DUSP1 serves as a pivotal regulator of diverse cellular processes such as proliferation, differentiation, apoptosis, autophagy, and stress responses. Emerging evidence highlights its context-dependent roles in cancer progression, where DUSP1 can function either as a tumor suppressor or promoter depending on the tumor type, stage, and tumor microenvironment (TME). Aberrant DUSP1 regulation is implicated in modulating cancer cell resistance to chemotherapy and radiotherapy, as well as facilitating immune evasion within the TME. This review provides a comprehensive overview of DUSP1, including molecular, structural, and regulatory mechanisms; its role in tumorigenesis, drug resistance, and immune modulation; and its therapeutic potential in precision oncology.