Gamma-interferon-inducible protein Ifi-16 (Ifi-16) also known as interferon-inducible myeloid differentiation transcriptional activator is a protein that in humans is encoded by the IFI16gene.[1][2][3]
This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53,[4][5]retinoblastoma-1 and BRCA1.[6] It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway.[3] IFI16 has been shown to play a role in the sensing of intracellular DNA[7] - a hallmark of virally infected cells - and has also been linked to the death of HIV-infected helper CD4 T cells by pyroptosis, a highly inflammatory form of programmed cell death.[8][9]
References
↑Trapani JA, Browne KA, Dawson MJ, Ramsay RG, Eddy RL, Show TB, White PC, Dupont B (Oct 1992). "A novel gene constitutively expressed in human lymphoid cells is inducible with interferon-gamma in myeloid cells". Immunogenetics. 36 (6): 369–76. doi:10.1007/bf00218044. PMID1526658.
↑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): 415–24. doi:10.1007/bf00177824. PMID7959953.
↑Ouchi, Mutsuko; Ouchi, Toru (2008-01-01). "Role of IFI16 in DNA damage and checkpoint". Frontiers in Bioscience. 13: 236–239. doi:10.2741/2673. ISSN1093-9946. PMID17981541.
Dawson MJ, Trapani JA (1995). "IFI 16 gene encodes a nuclear protein whose expression is induced by interferons in human myeloid leukaemia cell lines". J. Cell. Biochem. 57 (1): 39–51. doi:10.1002/jcb.240570106. PMID7536752.
Dawson MJ, Trapani JA, Briggs RC, et al. (1995). "The closely linked genes encoding the myeloid nuclear differentiation antigen (MNDA) and IFI16 exhibit contrasting haemopoietic expression". Immunogenetics. 41 (1): 40–3. doi:10.1007/BF00188431. PMID7806273.
Johnstone RW, Kerry JA, Trapani JA (1998). "The human interferon-inducible protein, IFI 16, is a repressor of transcription". J. Biol. Chem. 273 (27): 17172–7. doi:10.1074/jbc.273.27.17172. PMID9642285.
Johnstone RW, Kershaw MH, Trapani JA (1998). "Isotypic variants of the interferon-inducible transcriptional repressor IFI 16 arise through differential mRNA splicing". Biochemistry. 37 (34): 11924–31. doi:10.1021/bi981069a. PMID9718316.
Dawson MJ, Elwood NJ, Johnstone RW, Trapani JA (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". J. Leukoc. Biol. 64 (4): 546–54. PMID9766636.
Johnstone RW, Wei W, Greenway A, Trapani JA (2001). "Functional interaction between p53 and the interferon-inducible nucleoprotein IFI 16". Oncogene. 19 (52): 6033–42. doi:10.1038/sj.onc.1204005. PMID11146555.
Gariglio M, Azzimonti B, Pagano M, et al. (2003). "Immunohistochemical expression analysis of the human interferon-inducible gene IFI16, a member of the HIN200 family, not restricted to hematopoietic cells". J. Interferon Cytokine Res. 22 (7): 815–21. doi:10.1089/107999002320271413. PMID12184920.
Izmailova E, Bertley FM, Huang Q, et al. (2003). "HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages". Nat. Med. 9 (2): 191–7. doi:10.1038/nm822. PMID12539042.
Clarke CJ, Apostolidis V, Hii LL, et al. (2003). "Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16". J. Cell. Biochem. 89 (1): 80–93. doi:10.1002/jcb.10475. PMID12682910.
Xin H, Curry J, Johnstone RW, et al. (2003). "Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence". Oncogene. 22 (31): 4831–40. doi:10.1038/sj.onc.1206754. PMID12894224.
Kwak JC, Ongusaha PP, Ouchi T, Lee SW (2003). "IFI16 as a negative regulator in the regulation of p53 and p21(Waf1)". J. Biol. Chem. 278 (42): 40899–904. doi:10.1074/jbc.M308012200. PMID12925527.
Aglipay JA, Lee SW, Okada S, et al. (2004). "A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway". Oncogene. 22 (55): 8931–8. doi:10.1038/sj.onc.1207057. PMID14654789.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Raffaella R, Gioia D, De Andrea M, et al. (2004). "The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells". Exp. Cell Res. 293 (2): 331–45. doi:10.1016/j.yexcr.2003.10.014. PMID14729471.
Fujiuchi N, Aglipay JA, Ohtsuka T, et al. (2004). "Requirement of IFI16 for the maximal activation of p53 induced by ionizing radiation". J. Biol. Chem. 279 (19): 20339–44. doi:10.1074/jbc.M400344200. PMID14990579.
