title: Tumor Necrosis Factor Receptor Associated Factors (TRAFs) 2 and 3 Form a Transcriptional Complex with Phosho-RNA Polymerase II and p65 in CD40 Ligand Activated Neuro2a Cells.
abstract: The tumor necrosis factor receptor-associated factors (TRAFs) have been classically described as adaptor proteins that function as solely cytosolic signaling intermediates for the TNF receptor superfamily, Toll-like receptors (TLRs), NOD, like receptors (NLRs), cytokine receptors, and others. In this study, we show for the first time that TRAFs are present within the cytoplasm and nucleus of Neuro2a cells and primary cortical neurons, and that TRAF2 and TRAF3 translocate into the nucleus within minutes of CD40L stimulation. Analysis of the transcriptional regulatory potential of TRAFs by luciferase assay revealed that each of the TRAFs differentially functions as a transcriptional activator or repressor in a cell-specific manner. Interestingly, ChIP-qPCR data demonstrate that TRAFs 2/3, p65, and pRNAPol II form part of a transcriptional complex on the Icam-1 gene promoter upon CD40L stimulation. We further determined that TRAF2 recruitment to the nucleus is critical for the ubiquitination of H2b, a transcription permissive epigenetic modification. Our findings demonstrate for the first time that TRAFs 2/3 participate in the formation of a CD40L-induced transcriptional complex in neuronal cells.
authors: Department of Biochemistry and Molecular Biology, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors: Jimmy
authors: J
authors: El Hokayem
authors: Neuroscience Program, University of Miami, Miller School of Medicine, Miami, FL, USA.|The Miami Project to Cure Paralysis, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors: George C
authors: GC
authors: Brittain
authors: Department of Biochemistry and Molecular Biology, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors: Zafar
authors: Z
authors: Nawaz
authors: Neuroscience Program, University of Miami, Miller School of Medicine, Miami, FL, USA. jrb445@drexel.edu.|The Miami Project to Cure Paralysis, University of Miami, Miller School of Medicine, Miami, FL, USA. jrb445@drexel.edu.|Department of Biology, Drexel University, 3245 Chestnut Street, Philadelphia, PA, 19104, USA. jrb445@drexel.edu.
authors: John R
authors: JR
authors: Bethea
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000032:analysis / Q000378:metabolism*; D012319:RNA Polymerase II / Q000032:analysis / Q000378:metabolism*; D047992:TNF Receptor-Associated Factor 2 / Q000032:analysis / Q000378:metabolism*; D048008:TNF Receptor-Associated Factor 3 / Q000032:analysis / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D019013:CD40 Antigens; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; C000622387:TRAF2 protein, mouse; C063447:p65 oncofetal mRNA transport protein, rat; D012319:RNA Polymerase II
keywords: CD40; NF‐kB transcription factor; Neuron; Nucleus; TNF receptor associated factor (TRAF); Transcription; Tumor necrosis factor (TNF)