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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 IFI16 gene.[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]


  1. 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. PMID 1526658.
  2. 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. PMID 7959953.
  3. 3.0 3.1 "Entrez Gene: IFI16 interferon, gamma-inducible protein 16".
  4. Liao, Jack C. C.; Lam, Robert; Brazda, Vaclav; Duan, Shili; Ravichandran, Mani; Ma, Justin; Xiao, Ting; Tempel, Wolfram; Zuo, Xiaobing (2011-03-09). "Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53". Structure. 19 (3): 418–429. doi:10.1016/j.str.2010.12.015. ISSN 1878-4186. PMC 3760383. PMID 21397192.
  5. 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. ISSN 1093-9946. PMID 17981541.
  6. Dutta, Dipanjan; Dutta, Sujoy; Veettil, Mohanan Valiya; Roy, Arunava; Ansari, Mairaj Ahmed; Iqbal, Jawed; Chikoti, Leela; Kumar, Binod; Johnson, Karen E. (2015-06-01). "BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses". PLOS Pathogens. 11 (6): e1005030. doi:10.1371/journal.ppat.1005030. ISSN 1553-7374. PMC 4487893. PMID 26121674.
  7. Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, Sirois CM, Jin T, Latz E, Xiao TS, Fitzgerald KA, Paludan SR, Bowie AG (2010). "IFI16 is an innate immune sensor for intracellular DNA". Nat. Immunol. 11 (11): 997–1004. doi:10.1038/ni.1932. PMC 3142795. PMID 20890285.
  8. Monroe KM, Yang Z, Johnson JR, Geng X, Doitsh G, Krogan NJ, Greene WC (2014). "IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV". Science. 343 (6169): 428–32. doi:10.1126/science.1243640. PMC 3976200. PMID 24356113.
  9. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, Hunt PW, Hatano H, Sowinski S, Muñoz-Arias I, Greene WC (2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature. 505 (7484): 509–14. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.