Dusp13b, also known as TMDP, is an atypical dual-specificity phosphatase encoded by the DUSP13 gene. It inactivates stress-activated MAPKs in the order of selectivity JNK = p38>ERK in cells and suppresses AP-1-dependent gene expression, suggesting an important role in protecting spermatogenesis from external stress [1]. It has also been associated with other biological processes and disease-related pathways.

In NSCLC, itraconazole combined with osimertinib can inhibit the SHH/DUSP13B/p-STAT3 axis, reducing the proliferation and migration of osimertinib-resistant cells and promoting apoptosis. DUSP13B interacts with STAT3 and modulates its phosphorylation, and SHH, GLI1, p-STAT3, and DUSP13B play significant predictive roles in osimertinib resistance [2]. In cardiomyocytes, myogenin up-regulates DUSP13B, reducing apoptosis induced by reactive oxygen species through inactivating the p38 MAPK pathway [3].

In summary, Dusp13b is crucial in spermatogenesis protection, and its involvement in NSCLC drug resistance and cardiomyocyte apoptosis prevention reveals its importance in these biological and disease-related processes. Although no KO/CKO mouse model findings were presented, the studies suggest potential areas where such models could further clarify its functions and roles in diseases.

References:

1. Katagiri, Chiaki, Masuda, Kouhei, Nomura, Miyuki, Tanuma, Nobuhiro, Shima, Hiroshi. 2011. DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression. In Molecular and cellular biochemistry, 352, 155-62. doi:10.1007/s11010-011-0749-x. https://pubmed.ncbi.nlm.nih.gov/21360282/

2. Zheng, Hongmei, Tang, Yaoxiang, Zang, Hongjing, Ma, Jian, Fan, Songqing. 2024. Itraconazole Reversing Acquired Resistance to Osimertinib in NSCLC by Inhibiting the SHH/DUSP13B/p-STAT3 Axis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2409416. doi:10.1002/advs.202409416. https://pubmed.ncbi.nlm.nih.gov/39721017/

3. Luo, Jing, Gao, Qiang, Qiu, Hailong, Cen, Jianzheng, Zhuang, Jian. . Myogenin Regulates DUSP13 to Inhibit Apoptosis Induced by Reactive Oxygen Species. In Frontiers in bioscience (Landmark edition), 29, 49. doi:10.31083/j.fbl2902049. https://pubmed.ncbi.nlm.nih.gov/38420814/