The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA

Molecular Systems Biology

Volumn 11, Issue 2, 2015, Pages

  Diner, Benjamin A ^a   Li, Tuo ^a   Greco, Todd M ^a   Crow, Marni S ^a   Fuesler, John A ^a   Wang, Jennifer ^a   Cristea, Ileana M ^a  

^a PRINCETON UNIVERSITY   (United States)

Author keywords

DNA sensing; IFIX; innate immunity; interactome; PYHIN

Indexed keywords

DOUBLE STRANDED DNA; PROTEIN AIM2; PROTEIN IFI16; PROTEIN IFIX; PROTEIN MNDA; REGULATOR PROTEIN; UNCLASSIFIED DRUG; VIRUS DNA; AIM2 PROTEIN, HUMAN; DIFFERENTIATION ANTIGEN; DNA BINDING PROTEIN; IFI16 PROTEIN, HUMAN; IMMUNOLOGIC FACTOR; MNDA PROTEIN, HUMAN; NUCLEAR PROTEIN; PHOSPHOPROTEIN; PYHIN1 PROTEIN, HUMAN; RECOMBINANT PROTEIN; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR;

AMINO TERMINAL SEQUENCE; ANTIBODY AFFINITY; APOPTOSIS; ARTICLE; BIOINFORMATICS; CARBOXY TERMINAL SEQUENCE; CELL CYCLE ARREST; CELL NUCLEUS; CYTOPLASM; DNA DAMAGE; DNA REPAIR; HERPES SIMPLEX VIRUS 1; HUMAN; HUMAN CELL; IMMUNOREGULATION; INNATE IMMUNITY; INTRACELLULAR SIGNALING; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN DNA INTERACTION; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEOMICS; TRANSCRIPTION REGULATION; VIRUS REPLICATION; CHROMATIN IMMUNOPRECIPITATION; DNA SEQUENCE; GENETIC DATABASE; GENETICS; HEK293 CELL LINE; ISOLATION AND PURIFICATION; METABOLISM; MULTIGENE FAMILY; OPEN READING FRAME; SIGNAL TRANSDUCTION;

HERPESVIRIDAE;

ANTIGENS, DIFFERENTIATION, MYELOMONOCYTIC; CELL NUCLEUS; CHROMATIN IMMUNOPRECIPITATION; DATABASES, GENETIC; DNA, VIRAL; DNA-BINDING PROTEINS; HEK293 CELLS; HERPESVIRUS 1, HUMAN; HUMANS; IMMUNOLOGIC FACTORS; MULTIGENE FAMILY; NUCLEAR PROTEINS; OPEN READING FRAMES; PHOSPHOPROTEINS; PROTEOMICS; RECOMBINANT PROTEINS; RNA, SMALL INTERFERING; SEQUENCE ANALYSIS, DNA; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84923683601     PISSN: None     EISSN: 17444292     Source Type: Journal    
DOI: 10.15252/msb.20145808     Document Type: Article

References (121)

1. Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, Rohl I, Hopfner KP, Ludwig J, Hornung V, (2013a) cGAS produces a 2-5-linked cyclic dinucleotide second messenger that activates STING. Nature 498: 380-384
2. Ablasser A, Schmid-Burgk JL, Hemmerling I, Horvath GL, Schmidt T, Latz E, Hornung V, (2013b) Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature 503: 530-534
3. Ablasser A, Hemmerling I, Schmid-Burgk JL, Behrendt R, Roers A, Hornung V, (2014) TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. J Immunol 192: 5993-5997
4. Adamson AL, Kenney S, (2001) Epstein-barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies. J Virol 75: 2388-2399
5. Aglipay JA, Lee SW, Okada S, Fujiuchi N, Ohtsuka T, Kwak JC, Wang Y, Johnstone RW, Deng C, Qin J, Ouchi T, (2003) A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway. Oncogene 22: 8931-8938
6. 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: 4899-4913
7. Ansari MA, Singh VV, Dutta S, Veettil MV, Dutta D, Chikoti L, Lu J, Everly D, Chandran B, (2013) Constitutive interferon-inducible protein 16-inflammasome activation during Epstein-Barr virus latency I, II, and III in B and epithelial cells. J Virol 87: 8606-8623
8. Banumathy G, Somaiah N, Zhang R, Tang Y, Hoffmann J, Andrake M, Ceulemans H, Schultz D, Marmorstein R, Adams PD, (2009) Human UBN1 is an ortholog of yeast Hpc2p and has an essential role in the HIRA/ASF1a chromatin-remodeling pathway in senescent cells. Mol Cell Biol 29: 758-770
9. Berger MF, Philippakis AA, Qureshi AM, He FS, Estep PW 3rd, Bulyk ML, (2006) Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities. Nat Biotechnol 24: 1429-1435
10. Briggs RC, Atkinson JB, Miranda RN, (2005) Variable expression of human myeloid specific nuclear antigen MNDA in monocyte lineage cells in atherosclerosis. J Cell Biochem 95: 293-301
11. Burckstummer T, Baumann C, Bluml S, Dixit E, Durnberger G, Jahn H, Planyavsky M, Bilban M, Colinge J, Bennett KL, Superti-Furga G, (2009) An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol 10: 266-272
12. Chelbi-Alix MK, de The H, (1999) Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene 18: 935-941
13. Chen IF, Ou-Yang F, Hung JY, Liu JC, Wang H, Wang SC, Hou MF, Hortobagyi GN, Hung MC, (2006) AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model. Mol Cancer Ther 5: 1-7
14. Chlebowski A, Lubas M, Jensen TH, Dziembowski A, (2013) RNA decay machines: the exosome. Biochim Biophys Acta 1829: 552-560
15. Choi H, Larsen B, Lin ZY, Breitkreutz A, Mellacheruvu D, Fermin D, Qin ZS, Tyers M, Gingras AC, Nesvizhskii AI, (2011) SAINT: probabilistic scoring of affinity purification-mass spectrometry data. Nat Methods 8: 70-73
16. Choi H, Liu G, Mellacheruvu D, Tyers M, Gingras AC, Nesvizhskii AI, (2012) Analyzing protein-protein interactions from affinity purification-mass spectrometry data with SAINT. Curr Protoc Bioinformatics Chapter 8: Unit8 15
17. Cresswell KS, Clarke CJ, Jackson JT, Darcy PK, Trapani JA, Johnstone RW, (2005) Biochemical and growth regulatory activities of the HIN-200 family member and putative tumor suppressor protein, AIM2. Biochem Biophys Res Commun 326: 417-424
18. Cridland JA, Curley EZ, Wykes MN, Schroder K, Sweet MJ, Roberts TL, Ragan MA, Kassahn KS, Stacey KJ, (2012) The mammalian PYHIN gene family: phylogeny, evolution and expression. BMC Evol Biol 12: 140
19. Cristea IM, Williams R, Chait BT, Rout MP, (2005) Fluorescent proteins as proteomic probes. Mol Cell Proteomics 4: 1933-1941
20. Cristea IM, Moorman NJ, Terhune SS, Cuevas CD, O'Keefe ES, Rout MP, Chait BT, Shenk T, (2010) Human cytomegalovirus pUL83 stimulates activity of the viral immediate-early promoter through its interaction with the cellular IFI16 protein. J Virol 84: 7803-7814
21. Cuchet-Lourenco D, Anderson G, Sloan E, Orr A, Everett RD, (2013) The viral ubiquitin ligase ICP0 is neither sufficient nor necessary for degradation of the cellular DNA sensor IFI16 during herpes simplex virus 1 infection. J Virol 87: 13422-13432
22. Dawson MJ, Trapani JA, Briggs RC, Nicholl JK, Sutherland GR, Baker E, (1995) The closely linked genes encoding the myeloid nuclear differentiation antigen (MNDA) and IFI16 exhibit contrasting haemopoietic expression. Immunogenetics 41: 40-43
23. De Bustos C, Smits A, Strömberg B, Collins VP, Nistér M, Afink G, (2005) A PDGFRA promoter polymorphism, which disrupts the binding of ZNF148, is associated with primitive neuroectodermal tumours and ependymomas. J Med Genet 42: 31-37
24. Diner EJ, Burdette DL, Wilson SC, Monroe KM, Kellenberger CA, Hyodo M, Hayakawa Y, Hammond MC, Vance RE, (2013) The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep 3: 1355-1361
25. Ding Y, Wang L, Su LK, Frey JA, Shao R, Hunt KK, Yan DH, (2004) Antitumor activity of IFIX, a novel interferon-inducible HIN-200 gene, in breast cancer. Oncogene 23: 4556-4566
26. 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: 1979-1996
27. Djavani M, Rodas J, Lukashevich IS, Horejsh D, Pandolfi PP, Borden KL, Salvato MS, (2001) Role of the promyelocytic leukemia protein PML in the interferon sensitivity of lymphocytic choriomeningitis virus. J Virol 75: 6204-6208
28. Doucas V, Ishov AM, Romo A, Juguilon H, Weitzman MD, Evans RM, Maul GG, (1996) Adenovirus replication is coupled with the dynamic properties of the PML nuclear structure. Genes Dev 10: 196-207
29. Dufour F, Sasseville AM, Chabaud S, Massie B, Siegel RM, Langelier Y, (2011) The ribonucleotide reductase R1 subunits of herpes simplex virus types 1 and 2 protect cells against TNFalpha- and FasL-induced apoptosis by interacting with caspase-8. Apoptosis 16: 256-271
30. Duhl DM, Gaczynski M, Olinski R, Briggs RC, (1989) Intranuclear distribution of the human myeloid cell nuclear differentiation antigen in Hl-60 Cells. J Cell Physiol 141: 148-153
31. Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, Moscat J, (2008) The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 13: 343-354
32. Everett RD, Maul GG, (1994) HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO J 13: 5062-5069
33. 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: 10991-11004
34. Everett RD, Parada C, Gripon P, Sirma H, Orr A, (2008) Replication of ICP0-null mutant herpes simplex virus type 1 is restricted by both PML and Sp100. J Virol 82: 2661-2672
35. Fanis P, Gillemans N, Aghajanirefah A, Pourfarzad F, Demmers J, Esteghamat F, Vadlamudi RK, Grosveld F, Philipsen S, van Dijk TB, (2012) Five friends of methylated chromatin target of protein-arginine-methyltransferase[Prmt]-1 (Chtop), a complex linking arginine methylation to desumoylation. Mol Cell Proteomics 11: 1263-1273
36. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES, (2009) AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458: 509-513
37. Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S, Wu J, Datta P, McCormick M, Huang L, McDermott E, Eisenlohr L, Landel CP, Alnemri ES, (2010) The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol 11: 385-393
38. Fotouhi-Ardakani N, Kebir DE, Pierre-Charles N, Wang L, Ahern SP, Filep JG, Milot E, (2010) Role for myeloid nuclear differentiation antigen in the regulation of neutrophil apoptosis during sepsis. Am J Respir Crit Care Med 182: 341-350
39. Fujiuchi N, Aglipay JA, Ohtsuka T, Maehara N, Sahin F, Su GH, Lee SW, Ouchi T, (2004) Requirement of IFI16 for the maximal activation of p53 induced by ionizing radiation. J Biol Chem 279: 20339-20344
40. Gaczynski M, Briggs JA, Wedrychowski A, Olinski R, Uskokovic M, Lian JB, Stein GS, Briggs RC, (1990) cis-diamminedichloroplatinum(II) cross-linking of the human myeloid cell nuclear differentiation antigen to DNA in HL-60 cells following 1,25-dihydroxy vitamin D3-induced monocyte differentiation. Cancer Res 50: 1183-1188
41. Ge J, Gong YN, Xu Y, Shao F, (2012) Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc Natl Acad Sci USA 109: 6193-6198
42. Glass M, Everett RD, (2013) Components of promyelocytic leukemia nuclear bodies (ND10) act cooperatively to repress herpesvirus infection. J Virol 87: 2174-2185
43. Guise AJ, Greco TM, Zhang IY, Yu F, Cristea IM, (2012) Aurora B-dependent regulation of class IIa histone deacetylases by mitotic nuclear localization signal phosphorylation. Mol Cell Proteomics 11: 1220-1229
44. Haussler MR, Haussler CA, Jurutka PW, Thompson PD, Hsieh JC, Remus LS, Selznick SH, Whitfield GK, (1997) The vitamin D hormone and its nuclear receptor: molecular actions and disease states. J Endocrinol 154 (Suppl): S57-S73
45. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR, Latz E, Fitzgerald KA, (2009) AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458: 514-518
46. Ishikawa H, Barber GN, (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455: 674-678
47. Ishov AM, Maul GG, (1996) The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol 134: 815-826
48. 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: 4425-4431
49. Jakobsen MR, Bak RO, Andersen A, Berg RK, Jensen SB, Jin T, Laustsen A, Hansen K, Ostergaard L, Fitzgerald KA, Xiao TS, Mikkelsen JG, Mogensen TH, Paludan SR, (2013) From the Cover: IFI16 senses DNA forms of the lentiviral replication cycle and controls HIV-1 replication. Proc Natl Acad Sci USA 110: E4571-E4580
50. Jin T, Perry A, Jiang J, Smith P, Curry JA, Unterholzner L, Jiang Z, Horvath G, Rathinam VA, Johnstone RW, Hornung V, Latz E, Bowie AG, Fitzgerald KA, Xiao TS, (2012) Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity 36: 561-571
51. Jin T, Perry A, Smith P, Jiang J, Xiao TS, (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: 13225-13235
52. 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: 5005-5018
53. Johnson KE, Bottero V, Flaherty S, Dutta S, Singh VV, Chandran B, (2014) IFI16 Restricts HSV-1 Replication by Accumulating on the HSV-1 Genome, Repressing HSV-1 Gene Expression, and Directly or Indirectly Modulating Histone Modifications. PLoS Pathog 10: e1004503
54. Johnstone RW, Kerry JA, Trapani JA, (1998) The human interferon-inducible protein, IFI 16, is a repressor of transcription. J Biol Chem 273: 17172-17177
55. Johnstone RW, Trapani JA, (1999) Transcription and growth regulatory functions of the HIN-200 family of proteins. Mol Cell Biol 19: 5833-5838
56. Joshi P, Greco TM, Guise AJ, Luo Y, Yu F, Nesvizhskii AI, Cristea IM, (2013) The functional interactome landscape of the human histone deacetylase family. Mol Syst Biol 9: 672
57. Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B, (2011) IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection. Cell Host Microbe 9: 363-375
58. Kim D-B, DeLuca NA, (2002) Phosphorylation of transcription factor Sp1 during herpes simplex virus type 1 infection. J Virol 76: 6473-6479
59. Kim S, Bauernfeind F, Ablasser A, Hartmann G, Fitzgerald KA, Latz E, Hornung V, (2010) Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. Eur J Immunol 40: 1545-1551
60. Kondo Y, Nagai K, Nakahata S, Saito Y, Ichikawa T, Suekane A, Taki T, Iwakawa R, Enari M, Taniwaki M, Yokota J, Sakoda S, Morishita K, (2012) Overexpression of the DNA sensor proteins, absent in melanoma 2 and interferon-inducible 16, contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation. Cancer Sci 103: 782-790
61. Kondo T, Kobayashi J, Saitoh T, Maruyama K, Ishii KJ, Barber GN, Komatsu K, Akira S, Kawai T, (2013) DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING trafficking. Proc Natl Acad Sci USA 110: 2969-2974
62. Kramer T, Greco TM, Enquist LW, Cristea IM, (2011) Proteomic characterization of pseudorabies virus extracellular virions. J Virol 85: 6427-6441
63. Lallemand-Breitenbach V, de The H, (2010) PML nuclear bodies. Cold Spring Harb Perspect Biol 2: a000661
64. Law DJ, Tarlé SA, Merchant J, (1998) The human ZBP-89 homolog, located at chromosome 3q21, represses gastrin gene expression. Mamm Genome 9: 165-167
65. Lee J, Li L, Gretz N, Gebert J, Dihlmann S, (2012) Absent in melanoma 2 (AIM2) is an important mediator of interferon-dependent and -independent HLA-DRA and HLA-DRB gene expression in colorectal cancers. Oncogene 31: 1242-1253
66. Lee MN, Roy M, Ong SE, Mertins P, Villani AC, Li W, Dotiwala F, Sen J, Doench JG, Orzalli MH, Kramnik I, Knipe DM, Lieberman J, Carr SA, Hacohen N, (2013) Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach. Nat Immunol 14: 179-185
67. Li T, Diner BA, Chen J, Cristea IM, (2012) Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16. Proc Natl Acad Sci USA 109: 10558-10563
68. Li T, Chen J, Cristea IM, (2013) Human cytomegalovirus tegument protein pUL83 inhibits IFI16-mediated DNA sensing for immune evasion. Cell Host Microbe 14: 591-599
69. Liao JC, Lam R, Brazda V, Duan S, Ravichandran M, Ma J, Xiao T, Tempel W, Zuo X, Wang YX, Chirgadze NY, Arrowsmith CH, (2010) Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53. Structure 19: 418-429
70. Lilley CE, Chaurushiya MS, Boutell C, Everett RD, Weitzman MD, (2011) The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0. PLoS Pathog 7: e1002084
71. Llanos S, Serrano M, (2010) Depletion of ribosomal protein L37 occurs in response to DNA damage and activates p53 through the L11/MDM2 pathway. Cell Cycle 9: 4005-4012
72. Lombard DB, Guarente L, (2000) Nijmegen breakage syndrome disease protein and MRE11 at PML nuclear bodies and meiotic telomeres. Cancer Res 60: 2331-2334
73. Ludlow LE, Johnstone RW, Clarke CJ, (2005) The HIN-200 family: more than interferon-inducible genes? Exp Cell Res 308: 1-17
74. 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: 4026-4040
75. Luo Y, Li T, Yu F, Kramer T, Cristea IM, (2010) Resolving the composition of protein complexes using a MALDI LTQ Orbitrap. J Am Soc Mass Spectrom 21: 34-46
76. Mellacheruvu D, Wright Z, Couzens AL, Lambert JP, St-Denis NA, Li T, Miteva YV, Hauri S, Sardiu ME, Low TY, Halim VA, Bagshaw RD, Hubner NC, Al-Hakim A, Bouchard A, Faubert D, Fermin D, Dunham WH, Goudreault M, Lin ZY, et al, (2013) The CRAPome: a contaminant repository for affinity purification-mass spectrometry data. Nat Methods 10: 730-736
77. Merchant JL, Iyer GR, Taylor BR, Kitchen JR, Mortensen ER, Wang Z, Flintoft RJ, Michel JB, Bassel-Duby R, (1996) ZBP-89, a Krüppel-like zinc finger protein, inhibits epidermal growth factor induction of the gastrin promoter. Mol Cell Biol 16: 6644-6653
78. Mirzoeva OK, Petrini JH, (2001) DNA damage-dependent nuclear dynamics of the Mre11 complex. Mol Cell Biol 21: 281-288
79. Morgado-Palacin L, Llanos S, Serrano M, (2012) Ribosomal stress induces L11- and p53-dependent apoptosis in mouse pluripotent stem cells. Cell Cycle 11: 503-510
80. Morrone SR, Wang T, Constantoulakis LM, Hooy RM, Delannoy MJ, Sohn J, (2014) Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy. Proc Natl Acad Sci USA 111: E62-E71
81. Murray EL, Schoenberg DR, (2007) A+U-rich instability elements differentially activate 5-3 and 3-5 mRNA decay. Mol Cell Biol 27: 2791-2799
82. Muruve DA, Petrilli V, Zaiss AK, White LR, Clark SA, Ross PJ, Parks RJ, Tschopp J, (2008) The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452: 103-107
83. Orchard S, Ammari M, Aranda B, Breuza L, Briganti L, Broackes-Carter F, Campbell NH, Chavali G, Chen C, del-Toro N, Duesbury M, Dumousseau M, Galeota E, Hinz U, Iannuccelli M, Jagannathan S, Jimenez R, Khadake J, Lagreid A, Licata L, et al, (2014) The MIntAct project-IntAct as a common curation platform for 11 molecular interaction databases. Nucleic Acids Res 42: D358-D363
84. 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: E3008-E3017
85. Orzalli MH, Conwell SE, Berrios C, DeCaprio JA, Knipe DM, (2013) Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA. Proc Natl Acad Sci USA 110: E4492-E4501
86. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T, (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282: 24131-24145
87. Park HH, Lo YC, Lin SC, Wang L, Yang JK, Wu H, (2007) The death domain superfamily in intracellular signaling of apoptosis and inflammation. Annu Rev Immunol 25: 561-586
88. 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: 886-895
89. 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: 3237-3242
90. Rai TS, Puri A, McBryan T, Hoffman J, Tang Y, Pchelintsev NA, van Tuyn J, Marmorstein R, Schultz DC, Adams PD, (2011) Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex. Mol Cell Biol 31: 4107-4118
91. Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE, Waggoner L, Vanaja SK, Monks BG, Ganesan S, Latz E, Hornung V, Vogel SN, Szomolanyi-Tsuda E, Fitzgerald KA, (2010) The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol 11: 395-402
92. Reinholz M, Kawakami Y, Salzer S, Kreuter A, Dombrowski Y, Koglin S, Kresse S, Ruzicka T, Schauber J, (2013) HPV16 activates the AIM2 inflammasome in keratinocytes. Arch Dermatol Res 305: 723-732
93. Sagulenko V, Thygesen SJ, Sester DP, Idris A, Cridland JA, Vajjhala PR, Roberts TL, Schroder K, Vince JE, Hill JM, Silke J, Stacey KJ, (2013) AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death Differ 20: 1149-1160
94. Schattgen SA, Fitzgerald KA, (2011) The PYHIN protein family as mediators of host defenses. Immunol Rev 243: 109-118
95. Schwartz RA, Carson CT, Schuberth C, Weitzman MD, (2009) Adeno-associated virus replication induces a DNA damage response coordinated by DNA-dependent protein kinase. J Virol 83: 6269-6278
96. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T, (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13: 2498-2504
97. Singh VV, Kerur N, Bottero V, Dutta S, Chakraborty S, Ansari MA, Paudel N, Chikoti L, Chandran B, (2013) Kaposi's sarcoma-associated herpesvirus latency in endothelial and B cells activates gamma interferon-inducible protein 16-mediated inflammasomes. J Virol 87: 4417-4431
98. Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T, (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27: 431-432
99. Song LL, Alimirah F, Panchanathan R, Xin H, Choubey D, (2008) Expression of an IFN-inducible cellular senescence gene, IFI16, is up-regulated by p53. Mol Cancer Res 6: 1732-1741
100. Song LL, Ponomareva L, Shen H, Duan X, Alimirah F, Choubey D, (2010) Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates expression of human telomerase reverse transcriptase (hTERT) gene. PLoS ONE 5: e8569
101. Stoecklin G, Mayo T, Anderson P, (2006) ARE-mRNA degradation requires the 5-3 decay pathway. EMBO Rep 7: 72-77
102. Sun L, Wu J, Du F, Chen X, Chen ZJ, (2013) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339: 786-791
103. Sun C, Liu C, Dong J, Li D, Li W, (2014) Effects of the myeloid cell nuclear differentiation antigen on the proliferation, apoptosis and migration of osteosarcoma cells. Oncol Lett 7: 815-819
104. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, Jensen LJ, von Mering C, (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39: D561-D568
105. Tanaka Y, Chen ZJ, (2012) STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci Signal 5: ra20
106. Tavalai N, Papior P, Rechter S, Leis M, Stamminger T, (2006) Evidence for a role of the cellular ND10 protein PML in mediating intrinsic immunity against human cytomegalovirus infections. J Virol 80: 8006-8018
107. Thompson MR, Sharma S, Atianand M, Jensen SB, Carpenter S, Knipe DM, Fitzgerald KA, Kurt-Jones EA, (2014) Interferon gamma-inducible protein (IFI) 16 transcriptionally regulates type i interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses. J Biol Chem 289: 23568-23581
108. Tsai YC, Greco TM, Boonmee A, Miteva Y, Cristea IM, (2012) Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Mol Cell Proteomics 11: 60-76
109. 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: 997-1004
110. Vizcaino JA, Deutsch EW, Wang R, Csordas A, Reisinger F, Rios D, Dianes JA, Sun Z, Farrah T, Bandeira N, Binz PA, Xenarios I, Eisenacher M, Mayer G, Gatto L, Campos A, Chalkley RJ, Kraus HJ, Albar JP, Martinez-Bartolome S, et al, (2014) ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nat Biotechnol 32: 223-226
111. Weidtkamp-Peters S, Lenser T, Negorev D, Gerstner N, Hofmann TG, Schwanitz G, Hoischen C, Maul G, Dittrich P, Hemmerich P, (2008) Dynamics of component exchange at PML nuclear bodies. J Cell Sci 121: 2731-2743
112. Weiss M, Schrimpf S, Hengartner MO, Lercher MJ, von Mering C, (2010) Shotgun proteomics data from multiple organisms reveals remarkable quantitative conservation of the eukaryotic core proteome. Proteomics 10: 1297-1306
113. Wisniewski JR, Zougman A, Nagaraj N, Mann M, (2009) Universal sample preparation method for proteome analysis. Nat Methods 6: 359-362
114. Workman CT, Yin Y, Corcoran DL, Ideker T, Stormo GD, Benos PV, (2005) enoLOGOS: a versatile web tool for energy normalized sequence logos. Nucleic Acids Res 33: W389-W392
115. Wu J, Fernandes-Alnemri T, Alnemri ES, (2010) Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes. J Clin Immunol 30: 693-702
116. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ, (2013) Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339: 826-830
117. Xie J, Briggs JA, Briggs RC, (1998) Human hematopoietic cell specific nuclear protein MNDA interacts with the multifunctional transcription factor YY1 and stimulates YY1 DNA binding. J Cell Biochem 70: 489-506
118. Xin H, Pereira-Smith OM, Choubey D, (2004) Role of IFI 16 in cellular senescence of human fibroblasts. Oncogene 23: 6209-6217
119. Xu ZX, Timanova-Atanasova A, Zhao RX, Chang KS, (2003) PML colocalizes with and stabilizes the DNA damage response protein TopBP1. Mol Cell Biol 23: 4247-4256
120. Zhu Y, Poyurovsky MV, Li Y, Biderman L, Stahl J, Jacq X, Prives C, (2009) Ribosomal protein S7 is both a regulator and a substrate of MDM2. Mol Cell 35: 316-326
121. Zybailov BL, Florens L, Washburn MP, (2007) Quantitative shotgun proteomics using a protease with broad specificity and normalized spectral abundance factors. Mol BioSyst 3: 354-360