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The p50 and cRel NF-\u03baB subunits were found to be crucial for regulating genes important for dendritic cell-induced T cell responses (e.g., CD40, IL-12, and IL-18) but not for genes encoding inflammatory cytokines (e.g., TNF-\u03b1, IL-1\u03b1, and IL-6). In striking contrast, the RelA subunit was crucial for expression of inflammatory cytokine genes but not T cell stimulatory genes. These novel findings reveal a fundamentally important difference in biological function of genes regulated by different NF-\u03baB subunits. Focusing on RelA target gene specificity mechanisms, we investigated whether the \u03baB site and\/or the unique composition of RelA played the most crucial role. Surprisingly, studies of IL-6 expression showed that the \u03baB site is not a primary determinant of RelA target gene specificity. Instead, a major specificity mechanism is the unique ability of RelA to interact with the transcriptional coactivator CREB-binding protein, a function not shared with the closely related cRel subunit. Together, our findings indicate novel and critically important overall roles of NF-\u03baB in TLR-induced gene expression that are mediated by unique functions of distinct subunits.<\/jats:p>","DOI":"10.4049\/jimmunol.178.11.6777","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:24:11Z","timestamp":1397863451000},"page":"6777-6788","source":"Crossref","is-referenced-by-count":84,"title":["Distinct Roles of Different NF-\u03baB Subunits in Regulating Inflammatory and T Cell Stimulatory Gene Expression in Dendritic Cells"],"prefix":"10.1093","volume":"178","author":[{"given":"Junmei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida , Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida , Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida , Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shomyseh","family":"Sanjabi","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatah","family":"Ouaaz","sequence":"additional","affiliation":[{"name":"De\u0301partement de Biologie Cellulaire, Institut Cochin, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale Unite\u0301 567 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer A","family":"Beg","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, H. 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