| First Author | Liu H | Year | 2023 |
| Journal | Cell Death Differ | Pages | 1-13 |
| PubMed ID | 36681781 | Mgi Jnum | J:332894 |
| Mgi Id | MGI:7430643 | Doi | 10.1038/s41418-023-01116-1 |
| Citation | Liu H, et al. (2023) CD-NTase family member MB21D2 promotes cGAS-mediated antiviral and antitumor immunity. Cell Death Differ :1-13 |
| abstractText | cGAS/DncV-like nucleotidyltransferase (CD-NTase) family members are immune sensors that synthesize diverse nucleotide signals to initiate antiviral response in bacteria and animals. As a founding member of CD-NTase enzyme, cGAS has been identified as a key sensor for cytoplasmic DNA and type I interferons (IFNs) signaling in metazoan. However, the functions of other metazoan CD-NTases remain enigmatic. Here, we showed that Mab-21 domain-containing protein 2 (MB21D2), another member of the CD-NTase family, plays a positive role in modulating the cGAS-STING signaling in myeloid cells. Deficiency of MB21D2 in THP-1 cells or mice macrophages led to impaired production of type I interferon upon DNA stimulation. Consistently, Mb21d2(-/-) mice showed more susceptible to infection with DNA virus and faster growth of melanoma, compared to its counterparts. Mechanistically, MB21D2 specially bound with the N-terminal of cGAS, facilitated its liquid phase condensation and DNA-binding activity, leading to the enhanced production of cGAMP and subsequent IFN-beta production. Thus, our findings unveiled that the CD-NTase family member MB21D2 contributes to host antiviral and antitumor responses by enhancing cGAS activation. |
