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Gene Review

IFI16  -  interferon, gamma-inducible protein 16

Homo sapiens

Synonyms: Gamma-interferon-inducible protein 16, IFNGIP1, Ifi-16, Interferon-inducible myeloid differentiation transcriptional activator, PYHIN2
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Disease relevance of IFI16


High impact information on IFI16

  • In addition, one mouse gene in the Ifi-200 gene family and the human MNDA and IFI 16 genes show expression and/or regulation restricted to cells of the hematopoietic system, suggesting that these genes participate in blood cell-specific responses to interferons [5].
  • The IFI 16 gene is also located on human chromosome 1q [5].
  • In contrast, the prevalence of anti-IFI16 was 4% in patients with RA, 5% in those with chronic urticaria, and 13% in those with HCV infection [4].
  • OBJECTIVE: To investigate the presence and clinical significance of autoantibodies against the interferon-inducible gene IFI16 in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and other autoimmune diseases [4].
  • CONCLUSION: The results of this study provide evidence that an IFN-inducible gene, IFI16, may be involved in the pathophysiologic mechanisms of connective tissue disorders such as SSc [4].

Biological context of IFI16

  • These results suggest that loss of IFI16 results in deregulation of p53-mediated apoptosis, leading to cancer development [1].
  • In addition, we have localized AIM2 to the long arm of human chromosome 1 (band q22) in a highly conserved region which also contains the known interferon-inducible genes IFI16 and MNDA [6].
  • Androgen receptor auto-regulates its expression by a negative feedback loop through upregulation of IFI16 protein [2].
  • IFI16 consists of ten exons and nine intervening introns spanning at least 28 kilobases (kb) of DNA [7].
  • The human IFI16 gene is a member of an interferon-inducible family of mouse and human genes closely linked on syntenic regions of chromosome 1 [7].

Anatomical context of IFI16

  • IFNs alpha and gamma both induce IFI16 mRNA expression in myeloid cells [7].
  • Immunohistochemical analysis has demonstrated that the human IFI16 gene, in addition to the hematopoietic tissues, is highly expressed in endothelial cells and squamous stratified epithelia [8].
  • Moreover, overexpression of IFI 16 in immortalized fibroblasts strongly inhibited cell proliferation [9].
  • 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 [10].
  • IFI 16 was expressed in 100% of CD34+ cells isolated from human bone marrow [10].

Associations of IFI16 with chemical compounds

  • The induction of IFI16 protein in LNCaP cells was dependent on the duration of TSA treatment [11].
  • This pathway is a general response to ROS and not specific to H2O2 treatment, as two other ROS-generating compounds, i.e., S-nitroso-N-acetylpenicillamine and tert-butyl hydroperoxide, were equally capable to induce IFI16 [12].
  • To investigate the mechanism of IFI16 accumulation, cells were incubated for 6 h in the presence of H2O2 or IFN-beta, and then cycloheximide was added to inhibit further protein synthesis [12].
  • Induction of IFI16 by H2O2 was concentration- and time-dependent (maximum at 50 microM, 6 h after treatment) and down-regulated by pretreatment with N-acetyl-L-cysteine, which acts as an antioxidant [12].
  • In this study we compare the thermodynamic, folding and stability properties of different members of the PAAD and CARD families and investigate structural conformational changes induced by the helix inducers trifluoroethanol and SDS on the PAAD domain of IFI16 and on the CARD domain of RAIDD [13].

Physical interactions of IFI16

  • Nuclear IFI 16 was able to bind double-stranded DNA in vitro and exhibited a similar elution profile from DNA-cellulose as previously observed for MNDA and 204 [14].
  • Given that IFI 16 contains two MFHATVAT motifs, we sought to determine whether IFI 16 may form a complex with p53 and if so to ascertain the functional significance of this interaction [15].

Regulatory relationships of IFI16


Other interactions of IFI16


Analytical, diagnostic and therapeutic context of IFI16

  • An increase of IFI16 was accompanied by interaction with p53 phosphorylated at its N terminus, as shown by immunoprecipitation experiments [12].
  • Immunohistochemical detection of IFI16 in paraffin-embedded tissues is achieved by using a polyclonal antibody raised against its C-terminal fragment that recognizes its three closely migrating isoforms in Western blotting [18].
  • METHODS: Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry [3].
  • Levels of antibodies against IFI16 in sera from 82 patients with SSc and 100 patients with SLE were determined by enzyme-linked immunosorbent assay [4].
  • IFI 16 migrates on SDS-PAGE as three distinct protein species (IFI 16A, 16B, 16C) clustered at 85-95 kDa, and we therefore set out to determine the molecular mechanisms underpinning the production of these different isoforms [19].


  1. Requirement of IFI16 for the maximal activation of p53 induced by ionizing radiation. Fujiuchi, N., Aglipay, J.A., Ohtsuka, T., Maehara, N., Sahin, F., Su, G.H., Lee, S.W., Ouchi, T. J. Biol. Chem. (2004) [Pubmed]
  2. Androgen receptor auto-regulates its expression by a negative feedback loop through upregulation of IFI16 protein. Alimirah, F., Chen, J., Xin, H., Choubey, D. FEBS Lett. (2006) [Pubmed]
  3. Altered patterns of the interferon-inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation index. Azzimonti, B., Pagano, M., Mondini, M., De Andrea, M., Valente, G., Monga, G., Tommasino, M., Aluffi, P., Landolfo, S., Gariglio, M. Histopathology (2004) [Pubmed]
  4. A novel autoantigen to differentiate limited cutaneous systemic sclerosis from diffuse cutaneous systemic sclerosis: The interferon-inducible gene IFI16. Mondini, M., Vidali, M., Andrea, M.D., Azzimonti, B., Air??, P., D'Ambrosio, R., Riboldi, P., Meroni, P.L., Albano, E., Shoenfeld, Y., Gariglio, M., Landolfo, S. Arthritis Rheum. (2006) [Pubmed]
  5. The human myeloid cell nuclear differentiation antigen gene is one of at least two related interferon-inducible genes located on chromosome 1q that are expressed specifically in hematopoietic cells. Briggs, R.C., Briggs, J.A., Ozer, J., Sealy, L., Dworkin, L.L., Kingsmore, S.F., Seldin, M.F., Kaur, G.P., Athwal, R.S., Dessypris, E.N. Blood (1994) [Pubmed]
  6. Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma. DeYoung, K.L., Ray, M.E., Su, Y.A., Anzick, S.L., Johnstone, R.W., Trapani, J.A., Meltzer, P.S., Trent, J.M. Oncogene (1997) [Pubmed]
  7. 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. Trapani, J.A., Dawson, M., Apostolidis, V.A., Browne, K.A. Immunogenetics (1994) [Pubmed]
  8. The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells. Raffaella, R., Gioia, D., De Andrea, M., Cappello, P., Giovarelli, M., Marconi, P., Manservigi, R., Gariglio, M., Landolfo, S. Exp. Cell Res. (2004) [Pubmed]
  9. Role of IFI 16 in cellular senescence of human fibroblasts. Xin, H., Pereira-Smith, O.M., Choubey, D. Oncogene (2004) [Pubmed]
  10. 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. Dawson, M.J., Elwood, N.J., Johnstone, R.W., Trapani, J.A. J. Leukoc. Biol. (1998) [Pubmed]
  11. IFI16 in Human Prostate Cancer. Alimirah, F., Chen, J., Davis, F.J., Choubey, D. Mol. Cancer Res. (2007) [Pubmed]
  12. Up-regulation of the interferon-inducible IFI16 gene by oxidative stress triggers p53 transcriptional activity in endothelial cells. Gugliesi, F., Mondini, M., Ravera, R., Robotti, A., de Andrea, M., Gribaudo, G., Gariglio, M., Landolfo, S. J. Leukoc. Biol. (2005) [Pubmed]
  13. Thermodynamics and stability of the PAAD/DAPIN/PYRIN domain of IFI-16. Dalal, K., Pio, F. FEBS Lett. (2006) [Pubmed]
  14. IFI 16 gene encodes a nuclear protein whose expression is induced by interferons in human myeloid leukaemia cell lines. Dawson, M.J., Trapani, J.A. J. Cell. Biochem. (1995) [Pubmed]
  15. Functional interaction between p53 and the interferon-inducible nucleoprotein IFI 16. Johnstone, R.W., Wei, W., Greenway, A., Trapani, J.A. Oncogene (2000) [Pubmed]
  16. Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16. Clarke, C.J., Apostolidis, V., Hii, L.L., Gough, D.J., Trapani, J.A., Johnstone, R.W. J. Cell. Biochem. (2003) [Pubmed]
  17. The closely linked genes encoding the myeloid nuclear differentiation antigen (MNDA) and IFI16 exhibit contrasting haemopoietic expression. Dawson, M.J., Trapani, J.A., Briggs, R.C., Nicholl, J.K., Sutherland, G.R., Baker, E. Immunogenetics (1995) [Pubmed]
  18. Immunohistochemical expression analysis of the human interferon-inducible gene IFI16, a member of the HIN200 family, not restricted to hematopoietic cells. Gariglio, M., Azzimonti, B., Pagano, M., Palestro, G., De Andrea, M., Valente, G., Voglino, G., Navino, L., Landolfo, S. J. Interferon Cytokine Res. (2002) [Pubmed]
  19. Isotypic variants of the interferon-inducible transcriptional repressor IFI 16 arise through differential mRNA splicing. Johnstone, R.W., Kershaw, M.H., Trapani, J.A. Biochemistry (1998) [Pubmed]
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