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.[5][6][7]
Function
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,[8]retinoblastoma-1 and
BRCA1.[9] It modulates p53 function, and inhibits cell growth in the
Ras/Raf signaling pathway.[7] IFI16 has been shown to play a role in the sensing of intracellular
DNA[10] - 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.[11][12] Recently, it has been shown how IFI16, once extracellularly released, can induce inflammation upon
TLR4 binding, acting as a
DAMP.[13]
^"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, 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.
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^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.
S2CID2602156.
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.
doi:
10.1002/jlb.64.4.546.
PMID9766636.
S2CID40241172.
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.
S2CID26145639.
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.
S2CID32678644.
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.
S2CID21949316.
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.
hdl:2318/42932.
PMID14729471.