Dusp23, a dual-specificity protein phosphatase, contains a dual-specificity phosphatase catalytic (DSPc) domain. It has distinctive phosphatase activity towards p-nitrophenyl phosphate (pNPP), oligopeptides with phospho-tyrosine and phospho-threonine residues, and can dephosphorylate p44ERK1 in vitro [4]. It is involved in multiple biological processes, such as placental development by mediating GCM1 dephosphorylation and activation [5], and regulating cell-cell adhesion by promoting β-catenin dephosphorylation at Tyr 142 [6].

In systemic lupus erythematosus (SLE) patients, Dusp23 mRNA levels are higher in CD4+ T cells compared to healthy controls, and its expression is positively correlated with integrin subunit alpha L (ITGAL), perforin 1 (PRF1), CD40L, and DNA methylation-related enzymes (DNMTs) [1]. In calcium oxalate crystal-induced kidney fibrosis, Ezh2 inhibition reduces H3K27me3 enrichment on the Dusp23 gene promoter, elevating its expression, and DUSP23 mediates the dephosphorylation of pSMAD3 (Ser423/425), indicating Ezh2 promotes kidney fibrosis via the DUSP23/SMAD3 pathway [2]. High expression of Dusp23 in acute myeloid leukemia (AML) patients is associated with poor prognosis, and enrichment analysis suggests it may regulate important signal pathways in hematological tumors, including the MAPK pathways [3].

In conclusion, Dusp23 plays crucial roles in placental development, cell-cell adhesion, and is associated with diseases like SLE, kidney fibrosis, and AML. Research on Dusp23 using gene-based models helps to understand its functions in these biological processes and disease conditions, potentially providing new insights for disease treatment and prevention.

References:

1. Balada, E, Felip, L, Ordi-Ros, J, Vilardell-Tarrés, M. 2016. DUSP23 is over-expressed and linked to the expression of DNMTs in CD4+ T cells from systemic lupus erythematosus patients. In Clinical and experimental immunology, 187, 242-250. doi:10.1111/cei.12883. https://pubmed.ncbi.nlm.nih.gov/27737517/

2. Xia, Yuqi, Ye, Zehua, Li, Bojun, Zhou, Xiangjun, Cheng, Fan. 2025. EZH2-mediated macrophage-to-myofibroblast transition contributes to calcium oxalate crystal-induced kidney fibrosis. In Communications biology, 8, 286. doi:10.1038/s42003-025-07735-3. https://pubmed.ncbi.nlm.nih.gov/39987296/

3. Liu, Xi, Zhuang, Haihui, Li, Fenglin, Lu, Ying, Pei, Renzhi. 2024. Prognostic Significance of Dual-Specificity Phosphatase 23 Expression in Acute Myeloid Leukemia. In Journal of blood medicine, 15, 35-50. doi:10.2147/JBM.S437400. https://pubmed.ncbi.nlm.nih.gov/38344181/

4. Wu, Qihan, Li, Yao, Gu, Shaohua, Xie, Yi, Mao, Yumin. . Molecular cloning and characterization of a novel dual-specificity phosphatase 23 gene from human fetal brain. In The international journal of biochemistry & cell biology, 36, 1542-53. doi:. https://pubmed.ncbi.nlm.nih.gov/15147733/

5. Lin, Fang-Yu, Chang, Ching-Wen, Cheong, Mei-Leng, Chang, Geen-Dong, Chen, Hungwen. 2010. Dual-specificity phosphatase 23 mediates GCM1 dephosphorylation and activation. In Nucleic acids research, 39, 848-61. doi:10.1093/nar/gkq838. https://pubmed.ncbi.nlm.nih.gov/20855292/

6. Gallegos, Lisa Leon, Ng, Mei Rosa, Sowa, Mathew E, Harper, J Wade, Brugge, Joan S. 2016. A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for β-catenin. In Scientific reports, 6, 27114. doi:10.1038/srep27114. https://pubmed.ncbi.nlm.nih.gov/27255161/