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

Autor: Zafar Nawaz, John R. Bethea, George C. Brittain, Jimmy El Hokayem
Rok vydání: 2016
Předmět:
Transcriptional Activation
0301 basic medicine
TRAF3
Cytoplasm
Nucleocytoplasmic Transport Proteins
NF‐kB transcription factor
Neuroscience (miscellaneous)
Repressor
RNA polymerase II
Tumor necrosis factor (TNF)
Biology
Article
Nucleus
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
Transcription (biology)
Cell Line
Tumor
CD40
Animals
Humans
CD40 Antigens
Receptor
TNF receptor associated factor (TRAF)
Cell Nucleus
Genetics
TNF Receptor-Associated Factor 3
030102 biochemistry & molecular biology
Signal transducing adaptor protein
Promoter
Neuron
TNF Receptor-Associated Factor 2
Neoplasm Proteins
Cell biology
Mice
Inbred C57BL
HEK293 Cells
030104 developmental biology
Tumor Necrosis Factor Receptor-Associated Factors
Neurology
biology.protein
RNA Polymerase II
Transcription
Zdroj: Molecular Neurobiology
ISSN: 1559-1182
0893-7648
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1007/s12035-016-9742-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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