DUSP4, a dual-specificity phosphatase, is a key regulator in multiple biological pathways. It inactivates factors in the mitogen-activated protein kinase (MAPK) signaling cascade, such as extracellular signal-regulated kinase (ERK) 1/2 [3,4,5,6,8]. It also plays roles in innate immune signaling, regulating the activation of TBK1 and ERK1/2 in a complex with IRF3 to control type I interferon production [1]. Genetic models like KO mouse models are valuable for studying its functions.

In KO mouse models, DUSP4-deficient mice were more resistant to RNA and DNA virus infections but more susceptible to malaria parasites, indicating its role in nucleic acid sensor signaling and type I IFN regulation [1]. In esophageal squamous cell carcinoma, DUSP4 knockout in mice significantly inhibited 4-nitrochinoline-oxide-induced esophageal tumorigenesis, as DUSP4 promotes tumor progression by dephosphorylating HSP90β [2]. In endometroid carcinoma, ARID1A deficiency downregulates DUSP4, and ectopic DUSP4 expression decreased cell proliferation [4]. In clear cell renal cell carcinoma (CCRCC), DUSP4 silencing inhibited cell proliferation, migration, and tumorigenicity, and reversed autophagic activity changes induced by DUSP4 overexpression [7].

In conclusion, DUSP4 has diverse functions in regulating immune responses and cancer-related biological processes. The KO mouse models have been crucial in revealing its roles in virus-parasite resistance, esophageal and endometroid carcinoma, and CCRCC, providing insights into potential therapeutic targets for related diseases.