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Modulation of gene expression regulated by the transcription factor NF-κB/RelA.
Li, Xueling; Zhao, Yingxin; Tian, Bing; Jamaluddin, Mohammad; Mitra, Abhishek; Yang, Jun; Rowicka, Maga; Brasier, Allan R; Kudlicki, Andrzej.
Afiliación
  • Li X; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555; Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 7
  • Zhao Y; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555; Center for Clinical Proteomics, University of Texas Medical Branch, Galveston, Texas 77555.
  • Tian B; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555; Departments of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555.
  • Jamaluddin M; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555.
  • Mitra A; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555.
  • Yang J; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555; Departments of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555.
  • Rowicka M; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555; Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 7
  • Brasier AR; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555; Center for Clinical Proteomics, University of Texas Medical Branch, Galveston, Texas 77555; Departments o
  • Kudlicki A; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas 77555; Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555; Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 7
J Biol Chem ; 289(17): 11927-11944, 2014 Apr 25.
Article en En | MEDLINE | ID: mdl-24523406
Modulators (Ms) are proteins that modify the activity of transcription factors (TFs) and influence expression of their target genes (TGs). To discover modulators of NF-κB/RelA, we first identified 365 NF-κB/RelA-binding proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We used a probabilistic model to infer 8349 (M, NF-κB/RelA, TG) triplets and their modes of modulatory action from our combined LC-MS/MS and ChIP-Seq (ChIP followed by next generation sequencing) data, published RelA modulators and TGs, and a compendium of gene expression profiles. Hierarchical clustering of the derived modulatory network revealed functional subnetworks and suggested new pathways modulating RelA transcriptional activity. The modulators with the highest number of TGs and most non-random distribution of action modes (measured by Shannon entropy) are consistent with published reports. Our results provide a repertoire of testable hypotheses for experimental validation. One of the NF-κB/RelA modulators we identified is STAT1. The inferred (STAT1, NF-κB/RelA, TG) triplets were validated by LC-selected reaction monitoring-MS and the results of STAT1 deletion in human fibrosarcoma cells. Overall, we have identified 562 NF-κB/RelA modulators, which are potential drug targets, and clarified mechanisms of achieving NF-κB/RelA multiple functions through modulators. Our approach can be readily applied to other TFs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Factor de Transcripción ReIA Tipo de estudio: Prognostic_studies Idioma: En Revista: J Biol Chem Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Factor de Transcripción ReIA Tipo de estudio: Prognostic_studies Idioma: En Revista: J Biol Chem Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos