Dual-specificity phosphatase 1 (DUSP1)

Dual-specificity phosphatase 1 (DUSP1), also widely known as MAP kinase phosphatase 1 (MKP-1), is a nuclear enzyme that plays a pivotal role in the negative regulation of mitogen-activated protein kinase (MAPK) signaling pathways [8, 11]. It functions by dephosphorylating both threonine and tyrosine residues on activated MAPKs, including ERK, JNK, and p38, thereby limiting the duration and intensity of cellular signaling in response to stress, mitogens, and pro-inflammatory stimuli [3, 8, 13]. In oncological contexts, DUSP1 acts as a double-edged sword; while it is frequently overexpressed in cancers such as breast, prostate, and colon where it facilitates chemoresistance by inhibiting stress-induced apoptosis, it can act as a tumor suppressor in others like head and neck squamous cell carcinoma by restraining tumor-associated inflammation [3, 5, 10, 15]. Beyond cancer, DUSP1 is a central mediator of the anti-inflammatory effects of glucocorticoids, as its induction by these steroids suppresses the production of various pro-inflammatory cytokines [8, 16, 17]. Therapeutic interest revolves around developing small-molecule inhibitors, such as BCI or triptolide, to sensitize resistant tumors to chemotherapy or utilizing its expression profile as a biomarker for disease progression and treatment efficacy [1, 10, 14, 18, 22]. However, targeting DUSP1 carries risks of inducing excessive inflammatory responses or cytokine storms, reflecting its essential role in maintaining immune homeostasis [4, 9, 23].

Other names

MAP kinase phosphatase 1MKP-1MKP1CL100Dual specificity protein phosphatase hVH1Protein-tyrosine phosphatase CL100VH1

Direct inhibition of the DUSP1 phosphatase catalytic or allosteric sites to sustain activated MAP kinase signaling, or transcriptional induction through glucocorticoid receptor activation to suppress pro-inflammatory cytokine production.