Mb21d2, a member of the cGAS/DncV-like nucleotidyltransferase (CD-NTase) family, plays significant roles in immunity and cancer-related processes. It is involved in the cGAS-STING signaling pathway in myeloid cells, which is crucial for the body's antiviral and antitumor responses [1].

In functional studies, Mb21d2-deficient THP-1 cells or mouse macrophages showed impaired production of type I interferon upon DNA stimulation. Mb21d2 -/- mice were more susceptible to DNA virus infection and had faster-growing melanomas, indicating its positive role in modulating the cGAS-STING signaling [1]. In HNSCC, overexpression of wild-type or a Q311E mutant MB21D2 promoted a pro-oncogenic phenotype, including cell proliferation, colony formation, and migration/invasion, through enrichment of KRAS signaling [2].

In conclusion, Mb21d2 contributes to host antiviral and antitumor responses by enhancing cGAS activation. Its role in promoting a pro-oncogenic phenotype in HNSCC highlights its importance in cancer-related research. The study of Mb21d2 using gene knockout models, such as the Mb21d2 -/- mice, has provided valuable insights into its functions in immunity and cancer [1,2].

References:

1. Liu, Hansen, Yan, Zhenzhen, Zhu, Deyu, Zhao, Wei, Gao, Chengjiang. 2023. CD-NTase family member MB21D2 promotes cGAS-mediated antiviral and antitumor immunity. In Cell death and differentiation, 30, 992-1004. doi:10.1038/s41418-023-01116-1. https://pubmed.ncbi.nlm.nih.gov/36681781/

2. Gracilla, Daniel E, Korla, Praveen Kumar, Lai, Ming-Tsung, Liou, Wen-Shiung, Sheu, Jim Jinn-Chyuan. 2020. Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro-oncogenic phenotype in HNSCC. In Molecular oncology, 14, 3065-3082. doi:10.1002/1878-0261.12806. https://pubmed.ncbi.nlm.nih.gov/32979859/