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Functions and roles of IFIX, a member of the human HIN-200 family, in human diseases

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Abstract

Pyrin and hematopoietic expression, interferon-inducible nature, and nuclear localization (HIN) domain family member 1 (PYHIN1), also known as IFIX, belongs to the family of pyrin proteins. This family includes structurally and functionally related mouse (e.g., p202, p203, and p204 proteins) and human (e.g., the interferon-inducible protein 16, absent in melanoma 2 protein, myeloid cell nuclear differentiation antigen, and pyrin and HIN domain family 1 or IFIX) proteins. The IFIX protein belongs to the HIN-200 family of interferon-inducible proteins that have a 200-amino acid signature motif at their C-termini. The increased expression of pyrin proteins in most cell types inhibits cell cycle control and modulates cell survival. Consistent with this role for pyrin proteins, IFIX is a potential antiviral DNA sensor that is essential for immune responses, the detection of viral DNA in the nucleus and cytoplasm, and the binding of foreign DNA via its HIN domain in a sequence non-specific manner. By promoting the ubiquitination and subsequent degradation of MDM2, IFIX acts as a tumor suppressor, thereby leading to p53/TP53 stabilization, HDAC1 regulation via the ubiquitin–proteasome pathway, and tumor-cell-specific silencing of the maspin gene. These data demonstrate that the potential molecular mechanism(s) underlying the action of the IFIX protein might be associated with the development of human diseases, such as viral infections, malignant tumors, and autoimmune diseases. This review summarizes the current insights into IFIX functions and how its regulation affects the outcomes of various human diseases.

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Abbreviations

PRRs:

Pattern recognition receptors

IFNs:

Interferons

AIM2:

Absent in melanoma 2

IFI16:

Interferon-inducible protein 16

IFIX:

Interferon-inducible protein X

MNDA:

Myeloid cell nuclear differentiation antigen

PYHIN:

Pyrin and hematopoietic expression, interferon-inducible nature, and nuclear localization

PY:

Pyrin

NF-κB:

Nuclear factor-kappa B

IL:

Interleukin

HSV-1:

Herpes simplex virus 1

STING:

Stimulator of IFN genes

TBK1:

STING–TANK binding kinase 1

dsDNA:

Double-strand DNA

PML:

Promyelocytic leukemia

NBs:

Nuclear bodies

DDR:

DNA damage response

TNFα:

Tumor necrosis factor alpha

PYD:

Pyrin domain

NLS:

Nuclear localization signal

HPV:

Human papillomavirus

EMT:

Epithelial mesenchymal transition

SLE:

Systemic lupus erythematosus

ICAM-1:

Intercellular adhesion molecule 1

IFN-γ:

IFN-gamma

IRF3:

Interferon regulatory factor 3

References

  1. Brubaker SW, Bonham KS, Zanoni I et al (2015) Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol 33:257–290

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Howard TR, Cristea IM (2020) Interrogating host antiviral environments driven by nuclear DNA sensing: a multiomic perspective. Biomolecules 10(12):E1591

    PubMed  Google Scholar 

  3. Brennan K, Bowie AG (2010) Activation of host pattern recognition receptors by viruses. Curr Opin Microbiol 13(4):503–507

    CAS  PubMed  Google Scholar 

  4. Diner BA, Li T, Greco TM et al (2015) The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA. Mol Syst Biol 11(1):787

    PubMed  PubMed Central  Google Scholar 

  5. Diner BA, Lum KK, Cristea IM (2015) The emerging role of nuclear viral DNA sensors. J Biol Chem 290(44):26412–26421

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Fairbrother WJ, Gordon NC, Humke EW et al (2001) The PYRIN domain: a member of the death domain-fold superfamily. Protein Sci 10(9):1911–1918

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Jin T, Perry A, Smith P et al (2013) Structure of the absent in melanoma 2 (AIM2) pyrin domain provides insights into the mechanisms of AIM2 autoinhibition and inflammasome assembly. J Biol Chem 288(19):13225–13235

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Li T, Chen J, Cristea IM (2013) Human cytomegalovirus tegument protein pUL83 inhibits IFI16-mediated DNA sensing for immune evasion. Cell Host Microbe 14(5):591–599

    CAS  PubMed  Google Scholar 

  9. McConnell BB, Vertino PM (2004) TMS1/ASC: the cancer connection. Apoptosis 9(1):5–18

    CAS  PubMed  Google Scholar 

  10. Jin T, Perry A, Jiang J et al (2012) Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity 36(4):561–571

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Shaw N, Liu ZJ (2014) Role of the HIN domain in regulation of innate immune responses. Mol Cell Biol 34(1):2–15

    PubMed  PubMed Central  Google Scholar 

  12. Fernandes-Alnemri T, Yu JW, Datta P et al (2009) AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458(7237):509–513

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Hornung V, Ablasser A, Charrel-Dennis M et al (2009) AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458(7237):514–518

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Kumari P, Russo AJ, Shivcharan S et al (2020) AIM2 in health and disease: inflammasome and beyond. Immunol Rev 297(1):83–95

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Mondini M, Costa S, Sponza S et al (2010) The interferon-inducible HIN-200 gene family in apoptosis and inflammation: implication for autoimmunity. Autoimmunity 43(3):226–231

    CAS  PubMed  Google Scholar 

  16. Morrone SR, Wang T, Constantoulakis LM et al (2014) Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy. Proc Natl Acad Sci USA 111(1):E62-71

    CAS  PubMed  Google Scholar 

  17. Li T, Diner BA, Chen J et al (2012) Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16. Proc Natl Acad Sci USA 109(26):10558–10563

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Orzalli MH, DeLuca NA, Knipe DM (2012) Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein. Proc Natl Acad Sci USA 109(44):E3008–E3017

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Choubey D, Deka R, Ho SM (2008) Interferon-inducible IFI16 protein in human cancers and autoimmune diseases. Front Biosci 1(13):598–608

    Google Scholar 

  20. Ding Y, Wang L, Su LK et al (2004) Antitumor activity of IFIX, a novel interferon-inducible HIN-200 gene, in breast cancer. Oncogene 23(26):4556–4566

    CAS  PubMed  Google Scholar 

  21. Chen Q, Sun L, Chen ZJ (2016) Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat Immunol 17(10):1142–1149

    CAS  PubMed  Google Scholar 

  22. Everett RD, Chelbi-Alix MK (2007) PML and PML nuclear bodies: implications in antiviral defence. Biochimie 89(6–7):819–830

    CAS  PubMed  Google Scholar 

  23. Tavalai N, Papior P, Rechter S et al (2006) Evidence for a role of the cellular ND10 protein PML in mediating intrinsic immunity against human cytomegalovirus infections. J Virol 80(16):8006–8018

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Lukashchuk V, Everett RD (2010) Regulation of ICP0-null mutant herpes simplex virus type 1 infection by ND10 components ATRX and hDaxx. J Virol 84(8):4026–4040

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Rai TS, Puri A, McBryan T et al (2011) Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex. Mol Cell Biol 31(19):4107–4118

    PubMed  PubMed Central  Google Scholar 

  26. Glass M, Everett RD (2013) Components of promyelocytic leukemia nuclear bodies (ND10) act cooperatively to repress herpesvirus infection. J Virol 87(4):2174–2185

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Nakad R, Schumacher B (2016) DNA damage response and immune defense: links and mechanisms. Front Genet 7:147

    PubMed  PubMed Central  Google Scholar 

  28. Haque A, Koide N, Odkhuu E et al (2014) Mouse pyrin and HIN domain family member 1 (pyhin1) protein positively regulates LPS-induced IFN-β and NO production in macrophages. Innate Immun 20(1):40–48

    PubMed  Google Scholar 

  29. Massa D, Baran M, Bengoechea JA et al (2020) PYHIN1 regulates pro-inflammatory cytokine induction rather than innate immune DNA sensing in airway epithelial cells. J Biol Chem 295(14):4438–4450

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Haque A, Koide N, Odkhuu E, Tsolmongyn B, Naiki Y, Komatsu T, Yoshida T, Yokochi T (2014) Mouse pyrin and HIN domain family member 1 (pyhin1) protein positively regulates LPS-induced IFN-β and NO production in macrophages. Innate Immun 20(1):40–48. https://doi.org/10.1177/1753425913481636

    Article  CAS  PubMed  Google Scholar 

  31. Kerur N, Veettil MV, Sharma-Walia N et al (2011) IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection. Cell Host Microbe 9(5):363–375

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Johnson KE, Chikoti L, Chandran B (2013) Herpes simplex virus 1 infection induces activation and subsequent inhibition of the IFI16 and NLRP3 inflammasomes. J Virol 87(9):5005–5018

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Jakobsen MR et al (2013) IFI16 senses DNA forms of the lentiviral replication cycle and controls HIV-1 replication. Proc Natl Acad Sci USA 110(48):E4571–E4580

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Doucas V, Ishov AM, Romo A et al (1996) Adenovirus replication is coupled with the dynamic properties of the PML nuclear structure. Genes Dev 10(2):196–207

    CAS  PubMed  Google Scholar 

  35. Ishov AM, Maul GG (1996) The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol 134(4):815–826

    CAS  PubMed  Google Scholar 

  36. Ahn JH, Brignole EJ 3rd, Hayward GS (1998) Disruption of PML subnuclear domains by the acidic IE1 protein of human cytomegalovirus is mediated through interaction with PML and may modulate a RING finger-dependent cryptic transactivator function of PML. Mol Cell Biol 18(8):4899–4913

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Chelbi-Alix MK, de Thé H (1999) Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene 18(4):935–941

    CAS  PubMed  Google Scholar 

  38. Adamson AL, Kenney S (2001) Epstein-barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies. J Virol 75(5):2388–2399

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Everett RD, Murray J, Orr A, Preston CM (2007) Herpes simplex virus type 1 genomes are associated with ND10 nuclear substructures in quiescently infected human fibroblasts. J Virol 81(20):10991–11004

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Howard TR, Crow MS, Greco TM, Lum KK, Li T, Cristea IM (2021) The DNA sensor IFIX drives proteome alterations to mobilize nuclear and cytoplasmic antiviral responses, with its acetylation acting as a localization toggle. mSystems 6(3):e0039721

    PubMed  Google Scholar 

  41. Pierce AJ, Hu P, Han M, Ellis N, Jasin M (2001) Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells. Genes Dev 15(24):3237–3242

    CAS  PubMed  PubMed Central  Google Scholar 

  42. de Jager M, Wyman C, van Gent DC, Kanaar R (2002) DNA end-binding specificity of human Rad50/Mre11 is influenced by ATP. Nucleic Acids Res 30(20):4425–4431

    PubMed  PubMed Central  Google Scholar 

  43. Bosso M, Kirchhoff F (2020) Emerging role of PYHIN proteins as antiviral restriction factors. Viruses 12(12):1464. https://doi.org/10.3390/v12121464

    Article  CAS  PubMed Central  Google Scholar 

  44. Connolly DJ, Bowie AG (2014) The emerging role of human PYHIN proteins in innate immunity: implications for health and disease. Biochem Pharmacol 92(3):405–414. https://doi.org/10.1016/j.bcp.2014.08.031

    Article  CAS  PubMed  Google Scholar 

  45. Atashzar MR, Daryabor G, Kabelitz D, Kalantar K (2019) Pyrin and hematopoietic interferon-inducible nuclear protein domain proteins: innate immune sensors for cytosolic and nuclear DNA. Crit Rev Immunol 39(4):275–288. https://doi.org/10.1615/CritRevImmunol.2020033114

    Article  PubMed  Google Scholar 

  46. Cubillos-Angulo JM, Arriaga MB, Melo MGM, Silva EC, Alvarado-Arnez LE, de Almeida AS, Moraes MO, Moreira ASR, Lapa E Silva JR, Fukutani KF, Sterling TR, Hawn TR, Kritski AL, Oliveira MM, Andrade BB (2020) Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil. Int J Infect Dis 92:21–28. https://doi.org/10.1016/j.ijid.2019.12.013

    Article  CAS  PubMed  Google Scholar 

  47. Tong Y, Song Y, Deng S (2019) Combined analysis and validation for DNA methylation and gene expression profiles associated with prostate cancer. Cancer Cell Int 4(19):50. https://doi.org/10.1186/s12935-019-0753-x

    Article  Google Scholar 

  48. Fanis P, Gillemans N, Aghajanirefah A et al (2012) Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to desumoylation. Mol Cell Proteom 11(11):1263–1273

    Google Scholar 

  49. Crow MS, Cristea IM (2017) Human antiviral protein IFIX suppresses viral gene expression during Herpes Simplex Virus 1 (HSV-1) infection and is counteracted by virus-induced proteasomal degradation. Mol Cell Proteomics 16(4 suppl 1):S200–S214

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10(15):886–895

    CAS  PubMed  Google Scholar 

  51. Bosso M, Prelli Bozzo C, Hotter D et al (2020) Nuclear PYHIN proteins target the host transcription factor Sp1 thereby restricting HIV-1 in human macrophages and CD4+ T cells. PLoS Pathog 16(8):e1008752

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Hiller S, Kohl A, Fiorito F et al (2003) NMR structure of the apoptosis- and inflammation-related NALP1 pyrin domain. Structure 11(10):1199–1205

    CAS  PubMed  Google Scholar 

  53. Liepinsh E, Barbals R, Dahl E, Sharipo A, Staub E, Otting G (2003) The death-domain fold of the ASC PYRIN domain, presenting a basis for PYRIN/PYRIN recognition. J Mol Biol 332(5):1155–1163

    CAS  PubMed  Google Scholar 

  54. Reed JC, Doctor K, Rojas A et al (2003) Comparative analysis of apoptosis and inflammation genes of mice and humans. Genome Res 13(6B):1376–1388

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Stehlik C, Reed JC (2004) The PYRIN connection: novel players in innate immunity and inflammation. J Exp Med 200(5):551–558

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Albrecht M, Choubey D, Lengauer T (2005) The HIN domain of IFI-200 proteins consists of two OB folds. Biochem Biophys Res Commun 327(3):679–687

    CAS  PubMed  Google Scholar 

  57. Bochkarev A, Bochkareva E (2004) From RPA to BRCA2: lessons from single-stranded DNA binding by the OB-fold. Curr Opin Struct Biol 14(1):36–42

    CAS  PubMed  Google Scholar 

  58. Theobald DL, Mitton-Fry RM, Wuttke DS (2003) Nucleic acid recognition by OB-fold proteins. Annu Rev Biophys Biomol Struct 32:115–133

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Asefa B, Klarmann KD, Copeland NG, Gilbert DJ, Jenkins NA, Keller JR (2004) The interferon-inducible p200 family of proteins: a perspective on their roles in cell cycle regulation and differentiation. Blood Cells Mol Dis 32(1):155–167

    CAS  PubMed  Google Scholar 

  60. Ludlow LE, Johnstone RW, Clarke CJ (2005) The HIN-200 family: more than interferon-inducible genes? Exp Cell Res 308(1):1–17

    CAS  PubMed  Google Scholar 

  61. Gariglio M, Azzimonti B, Pagano M et al (2002) 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):815–821

    CAS  PubMed  Google Scholar 

  62. 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):331–345

    CAS  PubMed  Google Scholar 

  63. Wei W, Clarke CJ, Somers GR et al (2003) Expression of IFI 16 in epithelial cells and lymphoid tissues. Histochem Cell Biol 119(1):45–54

    CAS  PubMed  Google Scholar 

  64. Azzimonti B, Pagano M, Mondini M et al (2004) 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. Histopathology 45(6):560–572

    CAS  PubMed  Google Scholar 

  65. DeYoung KL, Ray ME, Su YA et al (1997) Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma. Oncogene 15(4):453–457

    CAS  PubMed  Google Scholar 

  66. Doggett KL, Briggs JA, Linton MF et al (2002) Retroviral mediated expression of the human myeloid nuclear antigen in a null cell line upregulates Dlk1 expression. J Cell Biochem 86(1):56–66

    CAS  PubMed  Google Scholar 

  67. 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):20339–20344

    CAS  PubMed  Google Scholar 

  68. Kulaeva OI, Draghici S, Tang L, Kraniak JM, Land SJ, Tainsky MA (2003) Epigenetic silencing of multiple interferon pathway genes after cellular immortalization. Oncogene 22(26):4118–4127

    CAS  PubMed  Google Scholar 

  69. Mori Y, Yin J, Rashid A et al (2001) Instabilotyping: comprehensive identification of frameshift mutations caused by coding region microsatellite instability. Cancer Res 61(16):6046–6049

    CAS  PubMed  Google Scholar 

  70. Pradhan A, Mijovic A, Mills K et al (2004) Differentially expressed genes in adult familial myelodysplastic syndromes. Leukemia 18(3):449–459

    CAS  PubMed  Google Scholar 

  71. Varambally S, Dhanasekaran SM, Zhou M et al (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419(6907):624–629

    CAS  Google Scholar 

  72. Kimchi A, Resnitzky D, Ber R, Gat G (1988) Recessive genetic deregulation abrogates c-myc suppression by interferon and is implicated in oncogenesis. Mol Cell Biol 8(7):2828–2836

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Johnstone RW, Trapani JA (1999) Transcription and growth regulatory functions of the HIN-200 family of proteins. Mol Cell Biol 19(9):5833–5838. https://doi.org/10.1128/mcb.19.9.5833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Choubey D (2000) P202: an interferon-inducible negative regulator of cell growth. J Biol Regul Homeost Agents 14(3):187–192

    CAS  PubMed  Google Scholar 

  75. Saadatzadeh MR, Elmi AN, Pandya PH et al (2017) The role of MDM2 in promoting genome stability versus instability. Int J Mol Sci 18(10):2216. https://doi.org/10.3390/ijms18102216

    Article  CAS  PubMed Central  Google Scholar 

  76. Joazeiro CA, Weissman AM (2000) RING finger proteins: mediators of ubiquitin ligase activity. Cell 102(5):549–552

    CAS  PubMed  Google Scholar 

  77. Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM (2000) Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 275(12):8945–8951

    CAS  PubMed  Google Scholar 

  78. Honda R, Tanaka H, Yasuda H (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420(1):25–27

    CAS  PubMed  Google Scholar 

  79. Barak Y, Juven T, Haffner R, Oren M (1993) mdm2 expression is induced by wild type p53 activity. EMBO J 12(2):461–468

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Picksley SM, Lane DP (1993) The p53-mdm2 autoregulatory feedback loop: a paradigm for the regulation of growth control by p53? BioEssays 15(10):689–690

    CAS  PubMed  Google Scholar 

  81. Jones SN, Roe AE, Donehower LA, Bradley A (1995) Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378(6553):206–208

    CAS  PubMed  Google Scholar 

  82. de Oca Luna RM, Wagner DS, Lozano G (1995) Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378(65):203–206

    Google Scholar 

  83. Deb SP (2003) Cell cycle regulatory functions of the human oncoprotein MDM2. Mol Cancer Res 1(14):1009–1016

    CAS  PubMed  Google Scholar 

  84. Ding Y, Lee JF, Lu H, Lee MH, Yan DH (2006) Interferon-inducible protein IFIXalpha1 functions as a negative regulator of HDM2. Mol Cell Biol 26(5):1979–1996

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Maass N, Biallek M, Rösel F et al (2002) Hypermethylation and histone deacetylation lead to silencing of the maspin gene in human breast cancer. Biochem Biophys Res Commun 297(1):125–128

    CAS  PubMed  Google Scholar 

  86. Domann FE, Rice JC, Hendrix MJ, Futscher BW (2000) Epigenetic silencing of maspin gene expression in human breast cancers. Int J Cancer 85(6):805–810

    CAS  PubMed  Google Scholar 

  87. Yamaguchi H, Ding Y, Lee JF et al (2008) Interferon-inducible protein IFIXalpha inhibits cell invasion by upregulating the metastasis suppressor maspin. Mol Carcinog 47(10):739–743

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Riva G, Biolatti M, Pecorari G, Dell’Oste V, Landolfo S (2019) PYHIN proteins and HPV: role in the pathogenesis of head and neck squamous cell carcinoma. Microorganisms 8(1):14

    PubMed Central  Google Scholar 

  89. Wang S, Li F, Fan H (2021) Interferon-inducible protein, IFIX, has tumor-suppressive effects in oral squamous cell carcinoma. Sci Rep 11(1):19593

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Franke WW, Schmid E, Osborn M, Weber K (1979) Intermediate-sized filaments of human endothelial cells. J Cell Biol 81(3):570–580

    CAS  PubMed  Google Scholar 

  91. Sen A, O'Malley K, Wang Z, Raj GV, Defranco DB, Hammes SR (2010) Paxillin regulates androgen- and epidermal growth factor-induced MAPK signaling and cell proliferation in prostate cancer cells. J Biol Chem 285(37):28787–28795. https://doi.org/10.1074/jbc.M110.134064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Andreoletti G, Ashton JJ, Coelho T, Willis C, Haggarty R, Gibson J, Holloway J, Batra A, Afzal NA, Beattie RM, Ennis S (2015) Exome analysis of patients with concurrent pediatric inflammatory bowel disease and autoimmune disease. Inflamm Bowel Dis 21(6):1229–1236. https://doi.org/10.1097/MIB.0000000000000381

    Article  PubMed  Google Scholar 

  93. Kantor DB, Palmer CD, Young TR, Meng Y, Gajdos ZK, Lyon H, Price AL, Pollack S, London SJ, Loehr LR, Smith LJ, Kumar R, Jacobs DR Jr, Petrini MF, O’Connor GT, White WB, Papanicolaou G, Burkart KM, Heckbert SR, Barr RG, Hirschhorn JN (2013) Replication and fine mapping of asthma-associated loci in individuals of African ancestry. Hum Genet 132(9):1039–47. https://doi.org/10.1007/s00439-013-1310-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kanteti R et al (2016) FAK and paxillin, two potential targets in pancreatic cancer. Oncotarget 7(21):31586–601

    PubMed  PubMed Central  Google Scholar 

  95. Mondini M, Costa S, Sponza S, Gugliesi F, Gariglio M, Landolfo S (2010) The interferon-inducible HIN-200 gene family in apoptosis and inflammation: implication for autoimmunity. Autoimmunity 43(3):226–231

    CAS  PubMed  Google Scholar 

  96. Choubey D, Duan X, Dickerson E et al (2010) Interferon-inducible p200-family proteins as novel sensors of cytoplasmic DNA: role in inflammation and autoimmunity. J Interferon Cytokine Res 30(6):371–380

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Kimkong I, Avihingsanon Y, Hirankarn N (2009) Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR. Lupus 18(12):1066–1072

    CAS  PubMed  Google Scholar 

  98. Choubey D, Panchanathan R (2008) Interferon-inducible Ifi200-family genes in systemic lupus erythematosus. Immunol Lett 119(1–2):32–41

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Rozzo SJ, Allard JD, Choubey D et al (2001) Evidence for an interferon-inducible gene, Ifi202, in the susceptibility to systemic lupus. Immunity 15(3):435–443

    CAS  PubMed  Google Scholar 

  100. Caposio P, Gugliesi F, Zannetti C et al (2007) A novel role of the interferon-inducible protein IFI16 as inducer of proinflammatory molecules in endothelial cells. J Biol Chem 282(46):33515–33529

    CAS  PubMed  Google Scholar 

  101. Kumari P, Saha I, Narayanan A et al (2017) Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways. Cell Death Dis 8(10):e3078

    PubMed  PubMed Central  Google Scholar 

  102. Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G (2015) Type I interferons in anticancer immunity. Nat Rev Immunol 15(7):405–414

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Editage (www.editage.cn) for English language editing.

Funding

This work was supported by grants from Chinese Postdoctoral Science Foundation (No: 2018M641872).

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SW and JB conceived the idea and wrote the manuscript.

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Correspondence to Shan Wang or Jie Bai.

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Wang, S., Bai, J. Functions and roles of IFIX, a member of the human HIN-200 family, in human diseases. Mol Cell Biochem 477, 771–780 (2022). https://doi.org/10.1007/s11010-021-04297-w

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