IFI16
Description
The IFI16 (interferon gamma inducible protein 16) is a protein-coding gene located on chromosome 1.
IFI16, also known as interferon-inducible myeloid differentiation transcriptional activator, is a protein encoded by the IFI16 gene in humans. It belongs to the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. IFI16 contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. It localizes to the nucleoplasm and nucleoli and interacts with p53, retinoblastoma-1, and BRCA1. IFI16 modulates p53 function, inhibits cell growth in the Ras/Raf signaling pathway, and plays a role in sensing intracellular DNA, a hallmark of virally infected cells. It has been linked to the death of HIV-infected helper CD4 T cells by pyroptosis, a highly inflammatory form of programmed cell death. IFI16 can induce inflammation upon TLR4 binding when released extracellularly, acting as a DAMP.
IFI16 binds double-stranded DNA, particularly supercoiled and cruciform structures. It is involved in transcriptional regulation, potentially acting as a repressor. IFI16 may regulate hematopoietic differentiation through unknown target genes. It controls cellular proliferation by modulating the activity of cell cycle regulators like p53/TP53 and the retinoblastoma protein. IFI16 might contribute to TP53-mediated transcriptional activation by enhancing TP53's DNA binding and influencing its phosphorylation. It seems involved in the energy-dependent activation of the ATM/AMPK/TP53 pathway linked to autophagy regulation. IFI16 might participate in TP53-mediated cell death involving BRCA1. It may contribute to the senescence of prostate epithelial cells. IFI16 plays a role in the innate immune response by recognizing viral dsDNA in the cytosol and possibly the nucleus. Upon binding viral DNA in the cytoplasm, it recruits TMEM173/STING and triggers the production of IFN-beta. IFI16 exhibits anti-inflammatory activity, inhibiting AIM2 inflammasome activation likely through its association with AIM2. It is proposed to bind viral DNA in the nucleus, such as Kaposi's sarcoma-associated herpesvirus, and induce the formation of a nuclear caspase-1-activating inflammasome via PYCARD interaction. IFI16 inhibits the replication of herpesviruses like human cytomegalovirus (HCMV), potentially by interfering with the promoter recruitment of Sp1 transcription factors. It is essential for activating the IRF3 signaling cascade during human herpes simplex virus 1 (HHV-1) infection, promoting heterochromatin formation on herpesviral DNA, and inhibiting viral immediate-early gene expression and replication. IFI16 participates in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.
IFI16 is also known as IFNGIP1, PYHIN2.
