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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
Journal article   Open access   Peer reviewed

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

Jimmy El Hokayem, George C Brittain, 4th, Zafar Nawaz and John R Bethea
Molecular neurobiology, v 54(2), pp 1301-1313
Mar 2017
DOI: https://doi.org/10.1007/s12035-016-9742-4
PMID: 26843107
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1007/s12035-016-9742-4View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals CD40 Antigens - analysis CD40 Antigens - metabolism Cell Line, Tumor Cell Nucleus - chemistry Cell Nucleus - metabolism Cytoplasm - chemistry Cytoplasm - metabolism HEK293 Cells Humans Mice Mice, Inbred C57BL Neoplasm Proteins - analysis Neoplasm Proteins - metabolism Nucleocytoplasmic Transport Proteins - analysis Nucleocytoplasmic Transport Proteins - metabolism RNA Polymerase II - analysis RNA Polymerase II - metabolism TNF Receptor-Associated Factor 2 - analysis TNF Receptor-Associated Factor 2 - metabolism TNF Receptor-Associated Factor 3 - analysis TNF Receptor-Associated Factor 3 - metabolism Transcriptional Activation - physiology
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.

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10 citations in Web of Science
11 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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