BRD4 mediates NF-κB-dependent epithelial-mesenchymal transition and pulmonary fibrosis via transcriptional elongation

American Journal of Physiology - Lung Cellular and Molecular Physiology

Volumn 311, Issue 6, 2016, Pages L1183-L1201

  Tian, Bing ^a,b   Zhao, Yingxin ^a,b   Sun, Hong ^a   Zhang, Yueqing ^a   Yang, Jun ^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)

Author keywords

Airway epithelial cells; BRD4; Fibrosis; Mesenchymal transition; Nuclear factor B

Indexed keywords

BRD4 PROTEIN; CYCLIN DEPENDENT KINASE 9; GAMMA INTERFERON; GRANULOCYTE COLONY STIMULATING FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; INTERLEUKIN 8; PATHOGEN ASSOCIATED MOLECULAR PATTERN; PROTEIN; RE1A PROTEIN; SMALL INTERFERING RNA; TOLL LIKE RECEPTOR 3; TRANSCRIPTION FACTOR SNAIL; TRANSCRIPTION FACTOR ZEB1; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; TWIST RELATED PROTEIN 1; UNCLASSIFIED DRUG; VASCULOTROPIN; BRD4 PROTEIN, HUMAN; BRD4 PROTEIN, MOUSE; NUCLEAR PROTEIN; PROTEIN BINDING; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR RELA;

AIRWAY EPITHELIUM CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL FRACTIONATION; COLUMNAR EPITHELIUM; COMPARATIVE STUDY; CONFOCAL MICROSCOPY; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; EXPERIMENTAL PULMONARY FIBROSIS; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMEDIATE EARLY GENE; IMMUNOFLUORESCENCE; IMMUNOFLUORESCENCE MICROSCOPY; LUNG FIBROSIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSCRIPTION ELONGATION; ANIMAL; BIOLOGICAL MODEL; C57BL MOUSE; CELL NUCLEUS; CHROMATIN IMMUNOPRECIPITATION; CYTOLOGY; DRUG EFFECTS; EPITHELIUM CELL; GENETIC EPIGENESIS; GENETICS; INNATE IMMUNITY; LUNG; MALE; METABOLISM; PHOSPHORYLATION; PROTEIN STABILITY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION;

ANIMALS; CELL NUCLEUS; CHROMATIN IMMUNOPRECIPITATION; CYCLIN-DEPENDENT KINASE 9; EPIGENESIS, GENETIC; EPITHELIAL CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; GENES, IMMEDIATE-EARLY; HUMANS; IMMUNITY, INNATE; LUNG; MALE; MICE, INBRED C57BL; MODELS, BIOLOGICAL; NF-KAPPA B; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN STABILITY; PROTEIN TRANSPORT; PULMONARY FIBROSIS; SIGNAL TRANSDUCTION; TRANSCRIPTION ELONGATION, GENETIC; TRANSCRIPTION FACTOR RELA; TRANSCRIPTION FACTORS; TRANSFORMING GROWTH FACTOR BETA;

EID: 85006257762     PISSN: 10400605     EISSN: 15221504     Source Type: Journal    
DOI: 10.1152/ajplung.00224.2016     Document Type: Article

References (81)

1. Al-Muhsen S, Johnson JR, Hamid Q. Remodeling in asthma. J Allergy Clin Immunol 128: 451-462, 2011.
2. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413: 732-738, 2001.
3. Bisgrove DA, Mahmoudi T, Henklein P, Verdin E. Conserved P-TEFbinteracting domain of BRD4 inhibits HIV transcription. Proc Natl Acad Sci USA 104: 13690-13695, 2007.
4. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 161: 1720-1745, 2000.
5. Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop—a motor of cellular plasticity in development and cancer? EMBO Rep 11: 670-677, 2010.
6. Brasier AR, Tian B, Jamaluddin M, Kalita MK, Garofalo RP, Lu M. RelA Ser276 phosphorylation-coupled Lys310 acetylation controls transcriptional elongation of inflammatory cytokines in respiratory syncytial virus infection. J Virol 85: 11752-11769, 2011.
7. Broekelmann TJ, Limper AH, Colby TV, McDonald JA. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci USA 88: 6642-6646, 1991.
8. Brown JD, Lin CY, Duan Q, Griffin G, Federation AJ, Paranal RM, Bair S, Newton G, Lichtman AH, Kung AL, Yang T, Wang H, Luscinskas FW, Croce KJ, Bradner JE, Plutzky J. NF-kappaB directs dynamic super enhancer formation in inflammation and atherogenesis. Mol Cell 56: 219-231, 2014.
9. Burke JR, Pattoli MA, Gregor KR, Brassil PJ, MacMaster JF, McIntyre KW, Yang X, Iotzova VS, Clarke W, Strnad J, Qiu Y, Zusi FC. BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J Biol Chem 278: 1450-1456, 2003.
10. Camelo A, Dunmore R, Sleeman MA, Clarke DL. The epithelium in idiopathic pulmonary fibrosis: breaking the barrier. Front Pharmacol 4: 173, 2014.
11. Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet LP, Hamid Q. Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol 111: 1293-1298, 2003.
12. Chang H, Liu Y, Xue M, Liu H, Du S, Zhang L, Wang P. Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition. Nucleic Acids Res 44: 2514-2527, 2016.
13. Choudhary S, Boldogh I, Brasier AR. Inside-out signaling pathways from nuclear reactive oxygen species control pulmonary innate immunity. J Innate Immun 8: 143-155, 2016.
14. Davies DE. The role of the epithelium in airway remodeling in asthma. Proc Am Thorac Soc 6: 678-682, 2009.
15. Delgado O, Kaisani AA, Spinola M, Xie XJ, Batten KG, Minna JD, Wright WE, Shay JW. Multipotent capacity of immortalized human bronchial epithelial cells. PLoS One 6: e22023, 2011.
16. Devaiah BN, Case-Borden C, Gegonne A, Hsu CH, Chen Q, Meerzaman D, Dey A, Ozato K, Singer DS. BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin. Nat Struct Mol Biol 23: 540-548, 2016.
17. Ding N, Hah N, Yu RT, Sherman MH, Benner C, Leblanc M, He M, Liddle C, Downes M, Evans RM. BRD4 is a novel therapeutic target for liver fibrosis. Proc Natl Acad Sci USA 112: 15713-15718, 2015.
18. Fahy O, Hammad H, Senechal S, Pestel J, Tonnel AB, Wallaert B, Tsicopoulos A. Synergistic effect of diesel organic extracts and allergen Der p 1 on the release of chemokines by peripheral blood mononuclear cells from allergic subjects: involvement of the MAP kinase pathway. Am J Respir Cell Mol Biol 23: 247-254, 2000.
19. Fang L, Choudhary S, Zhao Y, Edeh CB, Yang C, Boldogh I, Brasier AR. ATM regulates NF-kappaB-dependent immediate-early genes via RelA Ser 276 phosphorylation coupled to CDK9 promoter recruitment. Nucleic Acids Res 42: 8416-8432, 2014.
20. Fang L, Choudhary S, Tian B, Boldogh I, Yang C, Ivanciuc T, Ma Y, Garofalo RP, Brasier AR. Ataxia telangiectasia mutated kinase mediates NF-kappaB serine 276 phosphorylation and interferon expression via the IRF7-RIG-I amplification loop in paramyxovirus infection. J Virol 89: 2628-2642, 2015.
21. Fedorov IA, Wilson SJ, Davies DE, Holgate ST. Epithelial stress and structural remodelling in childhood asthma. Thorax 60: 389-394, 2005.
22. Fernandez IE, Eickelberg O. The impact of TGF-beta on lung fibrosis: from targeting to biomarkers. Proc Am Thorac Soc 9: 111-116, 2012.
23. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La TN, French CA, Wiest O, Kung AL, Knapp S, Bradner JE. Selective inhibition of BET bromodomains. Nature 468: 1067-1073, 2010.
24. Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, Latz E, Monks B, Pitha PM, Golenbock DT. LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med 198: 1043-1055, 2003.
25. Forbus J, Spratt H, Wiktorowicz J, Wu Z, Boldogh I, Denner L, Kurosky A, Brasier RC, Luxon B, Brasier AR. Functional analysis of the nuclear proteome of human A549 alveolar epithelial cells by HPLChigh resolution 2-D gel electrophoresis. Proteomics 6: 2656-2672, 2006.
26. Hackett TL, Warner SM, Stefanowicz D, Shaheen F, Pechkovsky DV, Murray LA, Argentieri R, Kicic A, Stick SM, Bai TR, Knight DA. Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1. Am J Respir Crit Care Med 180: 122-133, 2009.
27. Harris WT, Kelly DR, Zhou Y, Wang D, MacEwen M, Hagood JS, Clancy JP, Ambalavanan N, Sorscher EJ. Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. PLoS One 8: e70196, 2013.
28. Hattori N, Degen JL, Sisson TH, Liu H, Moore BB, Pandrangi RG, Simon RH, Drew AF. Bleomycin-induced pulmonary fibrosis in fibrinogen-null mice. J Clin Invest 106: 1341-1350, 2000.
29. Hiraga R, Kato M, Miyagawa S, Kamata T. Nox4-derived ROS signaling contributes to TGF-beta-induced epithelial-mesenchymal transition in pancreatic cancer cells. Anticancer Res 33: 4431-4438, 2013.
30. Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 364: 709-721, 2004.
31. Holgate ST, Holloway J, Wilson S, Bucchieri F, Puddicombe S, Davies DE. Epithelial-mesenchymal communication in the pathogenesis of chronic asthma. Proc Am Thorac Soc 1: 93-98, 2004.
32. Hu CP, Wu XR, Li QG, Sun ZW, Wang AP, Feng JT, Wang J. Proteomic analysis of NGF-induced transdifferentiation of adrenal medullary cells. Int J Mol Med 32: 347-354, 2013.
33. Huang C, Kolokoltsova OA, Yun NE, Seregin AV, Poussard AL, Walker AG, Brasier AR, Zhao Y, Tian B, de la Torre JC, Paessler S. Junin virus infection activates the type I interferon pathway in a RIG-Idependent manner. PLoS Negl Trop Dis 6: e1659, 2012.
34. Huang RY, Guilford P, Thiery JP. Early events in cell adhesion and polarity during epithelial-mesenchymal transition. J Cell Sci 125: 4417-4422, 2012.
35. Huber MA, Azoitei N, Baumann B, Grunert S, Sommer A, Pehamberger H, Kraut N, Beug H, Wirth T. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest 114: 569-581, 2004.
36. Huber MA, Beug H, Wirth T. Epithelial-mesenchymal transition: NFkappaB takes center stage. Cell Cycle 3: 1477-1480, 2004.
37. Hubner RH, Gitter W, El Mokhtari NE, Mathiak M, Both M, Bolte H, Freitag-Wolf S, Bewig B. Standardized quantification of pulmonary fibrosis in histological samples. Biotechniques 44: 507-511, 2008.
38. Ijaz T, Pazdrak K, Kalita M, Konig R, Choudhary S, Tian B, Boldogh I, Brasier AR. Systems biology approaches to understanding epithelial mesenchymal transition (EMT) in mucosal remodeling and signaling in asthma. World Allergy Organ J 7: 13, 2014.
39. Jang MK, Mochizuki K, Zhou M, Jeong HS, Brady JN, Ozato K. The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol Cell 19: 523-534, 2005.
40. Kaisani A, Delgado O, Fasciani G, Kim SB, Wright WE, Minna JD, Shay JW. Branching morphogenesis of immortalized human bronchial epithelial cells in three-dimensional culture. Differentiation 87: 119-126, 2014.
41. Kalita M, Tian B, Gao B, Choudhary S, Wood TG, Carmical JR, Boldogh I, Mitra S, Minna JD, Brasier AR. Systems approaches to modeling chronic mucosal inflammation. Biomed Res Int 2013: 505864, 2013.
42. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 119: 1420-1428, 2009.
43. Katsuno Y, Lamouille S, Derynck R. TGF-beta signaling and epithelialmesenchymal transition in cancer progression. Curr Opin Oncol 25: 76-84, 2013.
44. Kim HJ, Litzenburger BC, Cui X, Delgado DA, Grabiner BC, Lin X, Lewis MT, Gottardis MM, Wong TW, Attar RM, Carboni JM, Lee AV. Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail. Mol Cell Biol 27: 3165-3175, 2007.
45. Knight DA, Ernst M, Anderson GP, Moodley YP, Mutsaers SE. The role of gp130/IL-6 cytokines in the development of pulmonary fibrosis: critical determinants of disease susceptibility and progression? Pharmacol Ther 99: 327-338, 2003.
46. Korkaya H, Kim GI, Davis A, Malik F, Henry NL, Ithimakin S, Quraishi AA, Tawakkol N, D’Angelo R, Paulson AK, Chung S, Luther T, Paholak HJ, Liu S, Hassan KA, Zen Q, Clouthier SG, Wicha MS. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell 47: 570-584, 2012.
47. Lambrecht BN, Hammad H. The airway epithelium in asthma. Nat Med 18: 684-692, 2012.
48. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelialmesenchymal transition. Nat Rev Mol Cell Biol 15: 178-196, 2014.
49. Li CW, Xia W, Huo L, Lim SO, Wu Y, Hsu JL, Chao CH, Yamaguchi H, Yang NK, Ding Q, Wang Y, Lai YJ, LaBaff AM, Wu TJ, Lin BR, Yang MH, Hortobagyi GN, Hung MC. Epithelial-mesenchymal transition induced by TNF-alpha requires NF-kappaB-mediated transcriptional upregulation of Twist1. Cancer Res 72: 1290-1300, 2012.
50. Liu P, Jamaluddin M, Li K, Garofalo RP, Casola A, Brasier AR. 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, 2007.
51. McDonald OG, Wu H, Timp W, Doi A, Feinberg AP. Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition. Nat Struct Mol Biol 18: 867-874, 2011.
52. Minshall EM, Leung DY, Martin RJ, Song YL, Cameron L, Ernst P, Hamid Q. Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 17: 326-333, 1997.
53. Noble PW, Barkauskas CE, Jiang D. Pulmonary fibrosis: patterns and perpetrators. J Clin Invest 122: 2756-2762, 2012.
54. Nowak DE, Tian B, Brasier AR. Two-step cross-linking method for identification of NF-kappaB gene network by chromatin immunoprecipitation. Biotechniques 39: 715-725, 2005.
55. Nowak DE, Tian B, Jamaluddin M, Boldogh I, Vergara LA, Choudhary S, Brasier AR. 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, 2008.
56. O’Byrne PM, Pedersen S, Lamm CJ, Tan WC, Busse WW. Severe exacerbations and decline in lung function in asthma. Am J Respir Crit Care Med 179: 19-24, 2009.
57. Ramirez RD, Sheridan S, Girard L, Sato M, Kim Y, Pollack J, Peyton M, Zou Y, Kurie JM, Dimaio JM, Milchgrub S, Smith AL, Souza RF, Gilbey L, Zhang X, Gandia K, Vaughan MB, Wright WE, Gazdar AF, Shay JW, Minna JD. Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res 64: 9027-9034, 2004.
58. Roche WR, Beasley R, Williams JH, Holgate ST. Subepithelial fibrosis in the bronchi of asthmatics. Lancet 1: 520-524, 1989.
59. Saglani S, Payne DN, Zhu J, Wang Z, Nicholson AG, Bush A, Jeffery PK. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med 176: 858-864, 2007.
60. Shi J, Wang Y, Zeng L, Wu Y, Deng J, Zhang Q, Lin Y, Li J, Kang T, Tao M, Rusinova E, Zhang G, Wang C, Zhu H, Yao J, Zeng YX, Evers BM, Zhou MM, Zhou BP. Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigenesis in basal-like breast cancer. Cancer Cell 25: 210-225, 2014.
61. Siemens H, Jackstadt R, Hunten S, Kaller M, Menssen A, Gotz U, Hermeking H. miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle 10: 4256-4271, 2011.
62. Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovectormediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest 100: 768-776, 1997.
63. Sosic D, Richardson JA, Yu K, Ornitz DM, Olson EN. Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity. Cell 112: 169-180, 2003.
64. Tang X, Peng R, Ren Y, Apparsundaram S, Deguzman J, Bauer CM, Hoffman AF, Hamilton S, Liang Z, Zeng H, Fuentes ME, DeMartino JA, Kitson C, Stevenson CS, Budd DC. BET bromodomain proteins mediate downstream signaling events following growth factor stimulation in human lung fibroblasts and are involved in bleomycin-induced pulmonary fibrosis. Mol Pharmacol 83: 283-293, 2013.
65. Tang X, Peng R, Phillips JE, Deguzman J, Ren Y, Apparsundaram S, Luo Q, Bauer CM, Fuentes ME, DeMartino JA, Tyagi G, Garrido R, Hogaboam CM, Denton CP, Holmes AM, Kitson C, Stevenson CS, Budd DC. Assessment of Brd4 inhibition in idiopathic pulmonary fibrosis lung fibroblasts and in vivo models of lung fibrosis. Am J Pathol 183: 470-479, 2013.
66. Tian B, Nowak DE, Brasier AR. A TNF-induced gene expression program under oscillatory NF-kappaB control. BMC Genomics 6: 137, 2005.
67. Tian B, Nowak DE, Jamaluddin M, Wang S, Brasier AR. Identification of direct genomic targets downstream of the nuclear factor-kappaB transcription factor mediating tumor necrosis factor signaling. J Biol Chem 280: 17435-17448, 2005.
68. Tian B, Yang J, Brasier AR. Two-step cross-linking for analysis of protein-chromatin interactions. Methods Mol Biol 809: 105-120, 2012.
69. Tian B, Zhao Y, Kalita M, Edeh CB, Paessler S, Casola A, Teng MN, Garofalo RP, Brasier AR. 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, 2013.
70. Tian B, Li X, Kalita M, Widen SG, Yang J, Bhavnani SK, Dang B, Kudlicki A, Sinha M, Kong F, Wood TG, Luxon BA, Brasier AR. Analysis of the TGFbeta-induced program in primary airway epithelial cells shows essential role of NF-kappaB/RelA signaling network in type II epithelial mesenchymal transition. BMC Genomics 16: 529, 2015.
71. Tieu BC, Lee C, Sun H, Lejeune W, Recinos A 3rd, Ju X, Spratt H, Guo DC, Milewicz D, Tilton RG, Brasier AR. An adventitial IL-6/ MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice. J Clin Invest 119: 3637-3651, 2009.
72. Warshamana GS, Pociask DA, Fisher KJ, Liu JY, Sime PJ, Brody AR. Titration of non-replicating adenovirus as a vector for transducing active TGF-beta1 gene expression causing inflammation and fibrogenesis in the lungs of C57BL/6 mice. Int J Exp Pathol 83: 183-201, 2002.
73. Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, du Bois RM, Borok Z. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol 166: 1321-1332, 2005.
74. Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem 282: 13141-13145, 2007.
75. Yang J, Mitra A, Dojer N, Fu S, Rowicka M, Brasier AR. A probabilistic approach to learn chromatin architecture and accurate inference of the NF-kappaB/RelA regulatory network using ChIP-Seq. Nucleic Acids Res 41: 7240-7259, 2013.
76. Zhang P, Dong Z, Cai J, Zhang C, Shen Z, Ke A, Gao D, Fan J, Shi G. BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma. Int J Immunopathol Pharmacol 28: 36-44, 2015.
77. Zhao Y, Jamaluddin M, Zhang Y, Sun H, Ivanucic T, Garofalo RP, Brasier AR. Systematic analysis of cell-type differences in the epithelial secretome reveals insights into pathogenesis of RSV-induced lower respiratory tract infections. J Immunol 2016.
78. Zhao Y, Widen SG, Jamaluddin M, Tian B, Wood TG, Edeh CB, Brasier AR. Quantification of activated NF-kappaB/RelA complexes using ssDNA aptamer affinity-stable isotope dilution-selected reaction monitoring-mass spectrometry. Mol Cell Proteomics 10: M111.008771, 2011.
79. Zhao Y, Brasier AR. Applications of selected reaction monitoring (SRM)-mass spectrometry (MS) for quantitative measurement of signaling pathways. Methods 61: 313-322, 2013.
80. Zhao Y, Tian B, Edeh CB, Brasier AR. Quantitation of the dynamic profiles of the innate immune response using multiplex selected reaction monitoring-mass spectrometry. Mol Cell Proteomics 12: 1513-1529, 2013.
81. Zou Z, Huang B, Wu X, Zhang H, Qi J, Bradner J, Nair S, Chen LF. Brd4 maintains constitutively active NF-kappaB in cancer cells by binding to acetylated RelA. Oncogene 33: 2395-2404, 2014.