Gamma-interferon-inducible protein Ifi-16 (Ifi-16) also known asinterferon-inducible myeloid differentiation transcriptional activator is aprotein that in humans is encoded by theIFI16gene.[5][6][7]
This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family ofcytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to thenucleoplasm andnucleoli, and interacts withp53.[8] It modulates p53 function, and inhibits cell growth in theRas/Raf signaling pathway.[7] IFI16 has been shown to play a role in the sensing of intracellularDNA[9] - a hallmark of virally infected cells - and has also been linked to the death ofHIV-infectedhelper CD4 T cells bypyroptosis, a highly inflammatory form of programmed cell death.[10][11] Recently, it has been shown how IFI16, once extracellularly released, can induce inflammation uponTLR4 binding, acting as aDAMP.[12]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Trapani JA, Browne KA, Dawson MJ, Ramsay RG, Eddy RL, Show TB, et al. (Oct 1992). "A novel gene constitutively expressed in human lymphoid cells is inducible with interferon-gamma in myeloid cells".Immunogenetics.36 (6):369–376.doi:10.1007/bf00218044.PMID1526658.S2CID1196925.
^Trapani JA, Dawson M, Apostolidis VA, Browne KA (Dec 1994). "Genomic organization of IFI16, an interferon-inducible gene whose expression is associated with human myeloid cell differentiation: correlation of predicted protein domains with exon organization".Immunogenetics.40 (6):415–424.doi:10.1007/bf00177824.PMID7959953.S2CID2602156.
^Iannucci A, Caneparo V, Raviola S, Debernardi I, Colangelo D, et al. (2020) Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding. PLOS Pathogens 16(9): e1008811.https://doi.org/10.1371/journal.ppat.1008811
Dawson MJ, Trapani JA (January 1995). "IFI 16 gene encodes a nuclear protein whose expression is induced by interferons in human myeloid leukaemia cell lines".Journal of Cellular Biochemistry.57 (1):39–51.doi:10.1002/jcb.240570106.PMID7536752.S2CID3007802.
Dawson MJ, Trapani JA, Briggs RC, Nicholl JK, Sutherland GR, Baker E (1995). "The closely linked genes encoding the myeloid nuclear differentiation antigen (MNDA) and IFI16 exhibit contrasting haemopoietic expression".Immunogenetics.41 (1):40–43.doi:10.1007/BF00188431.PMID7806273.S2CID12788123.
Johnstone RW, Kershaw MH, Trapani JA (August 1998). "Isotypic variants of the interferon-inducible transcriptional repressor IFI 16 arise through differential mRNA splicing".Biochemistry.37 (34):11924–11931.doi:10.1021/bi981069a.PMID9718316.
Dawson MJ, Elwood NJ, Johnstone RW, Trapani JA (October 1998). "The IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte lineage, but is rapidly and markedly down-regulated in other myeloid precursor populations".Journal of Leukocyte Biology.64 (4):546–554.doi:10.1002/jlb.64.4.546.PMID9766636.S2CID40241172.
Johnstone RW, Wei W, Greenway A, Trapani JA (December 2000). "Functional interaction between p53 and the interferon-inducible nucleoprotein IFI 16".Oncogene.19 (52):6033–6042.doi:10.1038/sj.onc.1204005.PMID11146555.S2CID13273815.
Gariglio M, Azzimonti B, Pagano M, Palestro G, De Andrea M, Valente G, et al. (July 2002). "Immunohistochemical expression analysis of the human interferon-inducible gene IFI16, a member of the HIN200 family, not restricted to hematopoietic cells".Journal of Interferon & Cytokine Research.22 (7):815–821.doi:10.1089/107999002320271413.hdl:2318/39497.PMID12184920.
Izmailova E, Bertley FM, Huang Q, Makori N, Miller CJ, Young RA, et al. (February 2003). "HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages".Nature Medicine.9 (2):191–197.doi:10.1038/nm822.PMID12539042.S2CID26145639.
Clarke CJ, Apostolidis V, Hii LL, Gough DJ, Trapani JA, Johnstone RW (May 2003). "Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16".Journal of Cellular Biochemistry.89 (1):80–93.doi:10.1002/jcb.10475.PMID12682910.S2CID32678644.
Xin H, Curry J, Johnstone RW, Nickoloff BJ, Choubey D (July 2003). "Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence".Oncogene.22 (31):4831–4840.doi:10.1038/sj.onc.1206754.PMID12894224.S2CID21949316.
Raffaella R, Gioia D, De Andrea M, Cappello P, Giovarelli M, Marconi P, et al. (February 2004). "The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells".Experimental Cell Research.293 (2):331–345.doi:10.1016/j.yexcr.2003.10.014.hdl:2318/42932.PMID14729471.
