DUSP4, a dual-specificity phosphatase, is involved in regulating multiple cellular signaling pathways. It plays a crucial role in the innate immune response, modulating the RIG-I-and STING-mediated IRF3-type I IFN response by regulating the activation of TBK1 and ERK1/2 in a signaling complex [1]. It is also associated with the MAPK signaling pathway, which is involved in numerous cellular processes such as cell growth, differentiation, and apoptosis.

In gene knockout studies, DUSP4-deficient mice were more resistant to RNA and DNA virus infections but more susceptible to malaria parasites, highlighting its role as a regulator of nucleic acid sensor signaling [1]. In esophageal squamous cell carcinoma, knockdown of DUSP4 suppressed cell proliferation and PDX-derived organoid growth, and Dusp4 knockout in mice significantly inhibited 4-nitrochinoline-oxide-induced esophageal tumorigenesis, indicating its role in cancer progression [2]. Dual inactivation of DUSP4 and DUSP6 selectively impaired the growth of NRAS and BRAF mutant cells through hyperactivation of MAPK signaling [3]. ARID1A loss, which downregulates DUSP4, activates MAPK signaling, suggesting a tumor-suppressing role of DUSP4 in ARID1A-mutated cancers [4]. In clear cell renal cell carcinoma, DUSP4 silencing inhibited cell proliferation and migration, and in papillary thyroid carcinoma, knockdown of DUSP4 promoted autophagy and cell death, demonstrating its oncogenic role in these cancers [5,6].

In conclusion, DUSP4 is a key regulator in both the innate immune response and cancer-related processes. Gene knockout models in mice have been instrumental in uncovering its role in virus resistance, cancer progression, and autophagy regulation. Understanding DUSP4's functions provides insights into the mechanisms of innate immunity and cancer development, potentially guiding the development of new therapeutic strategies.