CD-NTase family member MB21D2 promotes cGAS-mediated antiviral and antitumor immunity.
Hansen LiuZhenzhen YanDeyu ZhuHaiyan XuFeng LiuTian ChenHonghai ZhangYi ZhengBingyu LiuLei ZhangWei ZhaoChengjiang GaoPublished in: Cell death and differentiation (2023)
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-β production. Thus, our findings unveiled that the CD-NTase family member MB21D2 contributes to host antiviral and antitumor responses by enhancing cGAS activation.
Keyphrases
- induced apoptosis
- dna binding
- nk cells
- circulating tumor
- dendritic cells
- cell free
- immune response
- oxidative stress
- single molecule
- transcription factor
- type diabetes
- acute myeloid leukemia
- bone marrow
- signaling pathway
- cell proliferation
- metabolic syndrome
- cell death
- small molecule
- endoplasmic reticulum stress
- high fat diet induced