Ataxia telangiectasia mutated kinase mediates NF-κB serine 276 phosphorylation and interferon expression via the IRF7-RIG-I amplification loop in paramyxovirus infection

Journal of Virology

Volumn 89, Issue 5, 2015, Pages 2628-2642

  Fang, Ling ^a   Choudhary, Sanjeev ^a,b   Tian, Bing ^a,b   Boldogh, Istvan ^a,b   Yang, Chunying ^c   Ivanciuc, Teodora ^a   Ma, Yinghong ^a   Garofalo, Roberto P ^a,b   Brasier, Allan R ^a,b  

^a University of Texas Medical Branch School of Medicine   (United States)

^b UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; HISTONE H2AX; I KAPPA B KINASE GAMMA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON; INTERFERON REGULATORY FACTOR 3; INTERFERON REGULATORY FACTOR 7; MITOGEN AND STRESS ACTIVATED KINASE 1; PROTEIN SERINE THREONINE KINASE; RETINOIC ACID INDUCIBLE PROTEIN I; SERINE; SINGLE STRANDED RNA; TRANSCRIPTION FACTOR RELA; UNCLASSIFIED DRUG; ATM PROTEIN, HUMAN; DDX58 PROTEIN, HUMAN; DEAD BOX PROTEIN; IRF7 PROTEIN, HUMAN; MITOGEN AND STRESS-ACTIVATED PROTEIN KINASE 1; S6 KINASE;

ANIMAL CELL; ARTICLE; CELL NUCLEUS; CONTROLLED STUDY; CYTOKINE RELEASE; DNA DAMAGE; EMBRYO; ENZYME ACTIVATION; GENE SILENCING; HUMAN; HUMAN CELL; INNATE IMMUNITY; MOUSE; NONHUMAN; OXIDATIVE STRESS; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; RESPIRATORY SYNCYTIAL VIRUS INFECTION; RNA REPLICATION; SENDAI VIRUS INFECTION; VIRUS PATHOGENESIS; VIRUS REPLICATION; BIOSYNTHESIS; CELL LINE; EPITHELIUM CELL; HUMAN RESPIRATORY SYNCYTIAL VIRUS; IMMUNOLOGY; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN PROCESSING; SENDAI VIRUS; VIROLOGY;

PARAMYXOVIRIDAE; RESPIRATORY SYNCYTIAL VIRUS; RICE STRIPE VIRUS; SENDAI VIRUS;

ATAXIA TELANGIECTASIA MUTATED PROTEINS; CELL LINE; DEAD-BOX RNA HELICASES; EPITHELIAL CELLS; GENE SILENCING; HUMANS; INTERFERON REGULATORY FACTOR-7; INTERFERONS; NF-KAPPA B; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; RESPIRATORY SYNCYTIAL VIRUSES; RIBOSOMAL PROTEIN S6 KINASES, 90-KDA; SENDAI VIRUS; VIRUS REPLICATION;

EID: 84922998464     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02458-14     Document Type: Article

References (79)

1. Glezen WP, Taber LH, Frank AL, Kasel JA. 1986. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 140:543-546.
2. Welliver RC. 2004. Respiratory syncytial virus infection: therapy and prevention. Paediatr Respir Rev 5(Suppl A):S127-S133. http://dx.doi.org/10.1016/S1526-0542(04)90024-3.
3. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D, Grijalva CG, Zhu Y, Szilagyi P. 2009. The burden of respiratory syncytial virus infection in young children. N Engl J Med 360:588-598. http://dx.doi.org/10.1056/NEJMoa0804877.
4. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O'Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Simoes EA, Rudan I, Weber MW, Campbell H. 2010. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375:1545-1555. http://dx.doi.org/10.1016/S0140-6736(10)60206-1.
5. Hall CB, Douglas RG, Jr, Schnabel KC, Geiman JM. 1981. Infectivity of respiratory syncytial virus by various routes of inoculation. Infect Immun 33:779-783.
6. Zhang L, Peeples ME, Boucher RC, Collins PL, Pickles RJ. 2002. Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology. J Virol 76:5654-5666. http://dx.doi.org/10.1128/JVI.76.11.5654-5666.2002.
7. Aherne W, Bird T, Court SD, Gardner PS, McQuillin J. 1970. Pathological changes in virus infections of the lower respiratory tract in children. J Clin Pathol 23:7-18. http://dx.doi.org/10.1136/jcp.23.1.7.
8. Welliver TP, Garofalo RP, Hosakote Y, Hintz KH, Avendano L, Sanchez K, Velozo L, Jafri H, Chavez-Bueno S, Ogra PL, McKinney L, Reed JL, Welliver RC, Sr. 2007. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J Infect Dis 195:1126-1136. http://dx.doi.org/10.1086/512615.
9. Liesman RM, Buchholz UJ, Luongo CL, Yang L, Proia AD, DeVincenzo JP, Collins PL, Pickles RJ. 2014. RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction. J Clin Invest 124:2219-2233. http://dx.doi.org/10.1172/JCI72948.
10. Tregoning JS, Schwarze J. 2010. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev 23:74-98. http://dx.doi.org/10.1128/CMR.00032-09.
11. Zorc JJ, Hall CB. 2010. Bronchiolitis: recent evidence on diagnosis and management. Pediatrics 125:342-349. http://dx.doi.org/10.1542/peds.2009-2092.
12. Garofalo RP, Patti J, Hintz KA, Hill V, Ogra PL, Welliver R. 2001. Macrophage inflammatory protein 1-alpha, and ot T-helper type 2 cytokines is associated with severe forms of bronchiolitis. J Infect Dis 184:393-399. http://dx.doi.org/10.1086/322788.
13. Garofalo R, Sabry M, Jamaluddin M, Yu RK, Casola A, Ogra PL, Brasier AR. 1996. Transcriptional activation of the interleukin-8 gene by respiratory syncytial virus infection in alveolar epithelial cells: nuclear translocation of the RelA transcription factor as a mechanism producing airway mucosal inflammation. J Virol 70:8773-8781.
14. Brasier AR, Tian B, Jamaluddin M, Kalita MK, Garofalo RP, Lu M. 2011. RelA Ser276 phosphorylation-coupled Lys310 acetylation controls transcriptional elongation of inflammatory cytokines in respiratory syncytial virus infection. J Virol 85:11752-11769. http://dx.doi.org/10.1128/JVI.05360-11.
15. Tian B, Zhang Y, Luxon BA, Garofalo RP, Casola A, Sinha M, Brasier AR. 2002. Identification of NF-B-dependent gene networks in respiratory syncytial virus-infected cells. J Virol 76:6800-6814. http://dx.doi.org/10.1128/JVI.76.13.6800-6814.2002.
16. Zhang Y, Luxon BA, Casola A, Garofalo RP, Jamaluddin M, Brasier AR. 2001. Expression of respiratory syncytial virus-induced chemokine gene networks in lower airway epithelial cells revealed by cDNA microarrays. J Virol 75:9044-9058. http://dx.doi.org/10.1128/JVI.75.19.9044-9058.2001.
17. Liu P, Jamaluddin M, Li K, Garofalo RP, Casola A, Brasier AR. 2007. Retinoic acid-inducible gene I mediates early antiviral response and Toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells. J Virol 81:1401-1411. http://dx.doi.org/10.1128/JVI.01740-06.
18. Bibeau-Poirier A, Servant MJ. 2008. Roles of ubiquitination in patternrecognition receptors and type I interferon receptor signaling. Cytokine 43:359-367. http://dx.doi.org/10.1016/j.cyto.2008.07.012.
19. Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O, Akira S. 2005. Cell type-specific involvement of RIG-I in antiviral response. Immunity 23: 19-28. http://dx.doi.org/10.1016/j.immuni.2005.04.010.
20. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S. 2005. IPS-1, an adaptor triggering RIG-I-and Mda5-mediated type I interferon induction. Nat Immunol 6:981-988. http://dx.doi.org/10.1038/ni1243.
21. Huang C, Kolokoltsova OA, Yun NE, Seregin AV, Poussard AL, Walker AG, Brasier AR, Zhao Y, Tian B, de la Torre JC, Paessler S. 2012. Junín virus infection activates the type I interferon pathway in a RIG-Idependent manner. PLoS Negl Trop Dis 6:e1659. http://dx.doi.org/10.1371/journal.pntd.0001659.
22. Yoneyama M, Fujita T. 2008. Structural mechanism of RNA recognition by the RIG-I-like receptors. Immunity 29:178-181. http://dx.doi.org/10.1016/j.immuni.2008.07.009.
23. Yount JS, Gitlin L, Moran TM, Lopez CB. 2008. MDA5 participates in the detection of paramyxovirus infection and is essential for the early activation of dendritic cells in response to Sendai Virus defective interfering particles. J Immunol 180:4910-4918. http://dx.doi.org/10.4049/jimmunol.180.7.4910.
24. Seth RB, Sun L, Ea CK, Chen ZJ. 2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122:669-682. http://dx.doi.org/10.1016/j.cell.2005.08.012.
25. Cai X, Chen J, Xu H, Liu S, Jiang QX, Halfmann R, Chen ZJ. 2014. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell 156:1207-1222. http://dx.doi.org/10.1016/j.cell.2014.01.063.
26. Grandvaux N, Servant MJ, ten Oever B, Sen GC, Balachandran S, Barber GN, Lin R, Hiscott J. 2002. Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J Virol 76:5532-5539. http://dx.doi.org/10.1128/JVI.76.11.5532-5539.2002.
27. Schoggins JW, Rice CM. 2011. Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol 1:519-525. http://dx.doi.org/10.1016/j.coviro.2011.10.008.
28. Sadler AJ, Williams BR. 2008. Interferon-inducible antiviral effectors. Nat Rev Immunol 8:559-568. http://dx.doi.org/10.1038/nri2314.
29. Der SD, Zhou A, Williams BR, Silverman RH. 1998. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA 95:15623-15628. http://dx.doi.org/10.1073/pnas.95.26.15623.
30. Smith PL, Lombardi G, Foster GR. 2005. Type I interferons and the innate immune response-more than just antiviral cytokines. Mol Immunol 42:869-877. http://dx.doi.org/10.1016/j.molimm.2004.11.008.
31. Thomas E, Gonzalez VD, Li Q, Modi AA, Chen W, Noureddin M, Rotman Y, Liang TJ. 2012. HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons. Gastroenterology 142:978-988. http://dx.doi.org/10.1053/j.gastro.2011.12.055.
32. Schneider WM, Chevillotte MD, Rice CM. 2014. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol 32:513-545. http://dx.doi.org/10.1146/annurev-immunol-032713-120231.
33. Balachandran S, Beg AA. 2011. Defining emerging roles for NF-kappaB in antivirus responses: revisiting the interferon-beta enhanceosome paradigm. PLoS Pathog 7:e1002165. http://dx.doi.org/10.1371/journal.ppat.1002165.
34. Honda K, Yanai H, Takaoka A, Taniguchi T. 2005. Regulation of the type I IFN induction: a current view. Int Immunol 17:1367-1378. http://dx.doi.org/10.1093/intimm/dxh318.
35. Lu R, Moore PA, Pitha PM. 2002. Stimulation of IRF-7 gene expression by tumor necrosis factor alpha: requirement for NFkappa B transcription factor and gene accessibility. J Biol Chem 277:16592-16598. http://dx.doi.org/10.1074/jbc.M111440200.
36. Bertolusso R, Tian B, Zhao Y, Vergara L, Sabree A, Iwanaszko M, Lipniacki T, Brasier AR, Kimmel M. 2014. Dynamic cross talk model of the epithelial innate immune response to double-stranded RNA stimulation: coordinated dynamics emerging from cell-level noise. PLoS One 9:e93396. http://dx.doi.org/10.1371/journal.pone.0093396.
37. Jamaluddin M, Tian B, Boldogh I, Garofalo RP, Brasier AR. 2009. Respiratory syncytial virus infection induces a reactive oxygen species-MSK1-phospho-Ser-276 RelA pathway required for cytokine expression. J Virol 83:10605-10615. http://dx.doi.org/10.1128/JVI.01090-09.
38. Jamaluddin M, Wang S, Boldogh I, Tian B, Brasier AR. 2007. TNFalpha-induced NF-kappaB/RelA Ser(276) phosphorylation and enhanceosome formation is mediated by an ROS-dependent PKAc pathway. Cell Signal 19:1419-1433. http://dx.doi.org/10.1016/j.cellsig.2007.01.020.
39. Fang L, Choudhary S, Zhao Y, Edeh CB, Yang C, Boldogh I, Brasier AR. 2014. ATM regulates NF-kappaB-dependent immediate-early genes via RelA Ser 276 phosphorylation coupled to CDK9 promoter recruitment. Nucleic Acids Res 42:8416-8432. http://dx.doi.org/10.1093/nar/gku529.
40. Liu P, Lu M, Tian B, Li K, Garofalo RP, Prusak D, Wood TG, Brasier AR. 2009. Expression of an IKKgamma splice variant determines IRF3 and canonical NF-kappaB pathway utilization in ssRNA virus infection. PLoS One 4:e8079. http://dx.doi.org/10.1371/journal.pone.0008079.
41. Ueba O. 1978. Respiratory syncytial virus. I. Concentration and purification of the infectious virus. Acta Med Okayama 32:265-272.
42. Foy E, Li K, Wang C, Sumpter R, Jr, Ikeda M, Lemon SM, Gale M, Jr. 2003. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300:1145-1148. http://dx.doi.org/10.1126/science.1082604.
43. Choudhary S, Boldogh S, Garofalo R, Jamaluddin M, Brasier AR. 2005. Respiratory syncytial virus influences NF-kappaB-dependent gene expression through a novel pathway involving MAP3K14/NIK expression and nuclear complex formation with NF-kappaB2. J Virol 79:8948-8959. http://dx.doi.org/10.1128/JVI.79.14.8948-8959.2005.
44. Tian B, Zhao Y, Kalita M, Edeh CB, Paessler S, Casola A, Teng MN, Garofalo RP, Brasier AR. 2013. CDK9-dependent transcriptional elongation in the innate interferon-stimulated gene response to respiratory syncytial virus infection in airway epithelial cells. J Virol 87:7075-7092. http://dx.doi.org/10.1128/JVI.03399-12.
45. Nowak DE, Tian B, Brasier AR. 2005. Two-step cross-linking method for identification of NF-kappaB gene network by chromatin immunoprecipitation. Biotechniques 39:715-725. http://dx.doi.org/10.2144/000112014.
46. Tian B, Yang J, Brasier AR. 2012. Two-step cross-linking for analysis of protein-chromatin interactions. Methods Mol Biol 809:105-120. http://dx.doi.org/10.1007/978-1-61779-376-9_7.
47. Foster KA, Oster CG, Mayer MM, Avery ML, Audus KL. 1998. Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism. Exp Cell Res 243:359-366. http://dx.doi.org/10.1006/excr.1998.4172.
48. Jamaluddin M, Wang S, Garofalo RP, Elliott T, Casola A, Baron S, Brasier AR. 2001. IFN-beta mediates coordinate expression of antigenprocessing genes in RSV-infected pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 280:L248-L257.
49. Lau A, Swinbank KM, Ahmed PS, Taylor DL, Jackson SP, Smith GC, O'Connor MJ. 2005. Suppression of HIV-1 infection by a small molecule inhibitor of theATMkinase. Nat Cell Biol 7:493-500. http://dx.doi.org/10.1038/ncb1250.
50. Bakkenist CJ, Kastan MB. 2003. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499-506. http://dx.doi.org/10.1038/nature01368.
51. Wu ZH, Shi Y, Tibbetts RS, Miyamoto S. 2006. Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science 311:1141-1146. http://dx.doi.org/10.1126/science.1121513.
52. van Attikum H, Gasser SM. 2009. Crosstalk between histone modifications during the DNA damage response. Trends Cell Biol 19:207-217. http://dx.doi.org/10.1016/j.tcb.2009.03.001.
53. Mah LJ, El-Osta A, Karagiannis TC. 2010. gammaH2AX: a sensitive molecular marker of DNA damage and repair. Leukemia 24:679-686. http://dx.doi.org/10.1038/leu.2010.6.
54. Ba X, Bacsi A, Luo J, Aguilera-Aguirre L, Zeng X, Radak Z, Brasier AR, Boldogh I. 2014. 8-oxoguanine DNA glycosylase-1 augments proinflammatory gene expression by facilitating the recruitment of site-specific transcription factors. J Immunol 192:2384-2394. http://dx.doi.org/10.4049/jimmunol.1302472.
55. Nowak DE, Tian B, Jamaluddin M, Boldogh I, Vergara LA, Choudhary S, Brasier AR. 2008. RelA Ser276 phosphorylation is required for activation of a subset of NF-kappaB-dependent genes by recruiting cyclindependent kinase 9/cyclin T1 complexes. Mol Cell Biol 28:3623-3638. http://dx.doi.org/10.1128/MCB.01152-07.
56. Haeberle HA, Takizawa R, Casola A, Brasier AR, Dieterich HJ, Van Rooijen N, Gatalica Z, Garofalo RP. 2002. Respiratory syncytial virusinduced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways. J Infect Dis 186:1199-1206. http://dx.doi.org/10.1086/344644.
57. Hosakote YM, Liu T, Castro SM, Garofalo RP, Casola A. 2009. Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes. Am J Respir Cell Mol Biol 41:348-357. http://dx.doi.org/10.1165/rcmb.2008-0330OC.
58. Lilley CE, Schwartz RA, Weitzman MD. 2007. Using or abusing: viruses and the cellular DNA damage response. Trends Microbiol 15:119-126. http://dx.doi.org/10.1016/j.tim.2007.01.003.
59. Rohaly G, Korf K, Dehde S, Dornreiter I. 2010. Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication control. J Virol 84:10727-10747. http://dx.doi.org/10.1128/JVI.00122-10.
60. Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. 2009. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol 83:117-127. http://dx.doi.org/10.1128/JVI.01515-08.
61. Bian T, Gibbs JD, Orvell C, Imani F. 2012. Respiratory syncytial virus matrix protein induces lung epithelial cell cycle arrest through a p53 dependent pathway. PLoS One 7:e38052. http://dx.doi.org/10.1371/journal.pone.0038052.
62. Reference deleted.
63. Lee JH, Paull TT. 2007. Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene 26:7741-7748. http://dx.doi.org/10.1038/sj.onc.1210872.
64. Jacobs JL, Coyne CB. 2013. Mechanisms of MAVS regulation at the mitochondrial membrane. J Mol Biol 425:5009-5019. http://dx.doi.org/10.1016/j.jmb.2013.10.007.
65. Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT. 2010. ATM activation by oxidative stress. Science 330:517-521. http://dx.doi.org/10.1126/science.1192912.
66. Stilmann M, Hinz M, Arslan SC, Zimmer A, Schreiber V, Scheidereit C. 2009. A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation. Mol Cell 36:365-378. http://dx.doi.org/10.1016/j.molcel.2009.09.032.
67. Brasier AR. 2008. The NF-κB signaling network: insights from systems approaches, p 119-135. In Brasier AR, Lemon SM, Garcia-Sastre A (ed), Cellular signaling and innate immune responses to RNA virus infections. American Society for Microbiology, Washington, DC.
68. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, III, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ. 2007. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316:1160-1166. http://dx.doi.org/10.1126/science.1140321.
69. Ning S, Huye LE, Pagano JS. 2005. Regulation of the transcriptional activity of the IRF7 promoter by a pathway independent of interferon signaling. J Biol Chem 280:12262-12270. http://dx.doi.org/10.1074/jbc.M404260200.
70. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ. 2011. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 146:448-461. http://dx.doi.org/10.1016/j.cell.2011.06.041.
71. Basagoudanavar SH, Thapa RJ, Nogusa S, Wang J, Beg AA, Balachandran S. 2011. Distinct roles for the NF-kappa B RelA subunit during antiviral innate immune responses. J Virol 85:2599-2610. http://dx.doi.org/10.1128/JVI.02213-10.
72. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S, Jung JU. 2007. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446:916-920. http://dx.doi.org/10.1038/nature05732.
73. Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K. 2007. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci USA 104:7500-7505. http://dx.doi.org/10.1073/pnas.0611551104.
74. Gatti RA, Becker-Catania S, Chun HH, Sun X, Mitui M, Lai CH, Khanlou N, Babaei M, Cheng R, Clark C, Huo Y, Udar NC, Iyer RK. 2001. The pathogenesis of ataxia-telangiectasia. Learning from a Rosetta Stone. Clin Rev Allergy Immunol 20:87-108. http://dx.doi.org/10.1385/CRIAI:20:1:87.
75. McKinnon PJ. 2004. ATM and ataxia telangiectasia. EMBO Rep 5:772-776. http://dx.doi.org/10.1038/sj.embor.7400210.
76. Taylor AM, Byrd PJ. 2005. Molecular pathology of ataxia telangiectasia. J Clin Pathol 58:1009-1015. http://dx.doi.org/10.1136/jcp.2005.026062.
77. Shiloh Y. 2003. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 3:155-168. http://dx.doi.org/10.1038/nrc1011.
78. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. 2004. Immunodeficiency and infections in ataxiatelangiectasia. J Pediatr 144:505-511. http://dx.doi.org/10.1016/j.jpeds.2003.12.046.
79. Staples ER, McDermott EM, Reiman A, Byrd PJ, Ritchie S, Taylor AM, Davies EG. 2008. Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene. Clin Exp Immunol 153:214-220. http://dx.doi.org/10.1111/j.1365-2249.2008.03684.x.