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- Table of Contents
Facts about TNF receptor-associated factor 1.
The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin-protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14. The TRAF1/TRAF2 complex recruits the antiapoptotic E3 protein- ubiquitin ligases BIRC2 and BIRC3 to TNFRSF1B/TNFR2.
Human | |
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Gene Name: | TRAF1 |
Uniprot: | Q13077 |
Entrez: | 7185 |
Belongs to: |
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No superfamily |
EBI6; EBI6MGC:10353; Epstein-Bar virus-induced protein 6; Epstein-Barr virus-induced protein 6; TNF receptor-associated factor 1; TRAF1; TRAF-1
Mass (kDA):
46.164 kDA
Human | |
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Location: | 9q33.2 |
Sequence: | 9; NC_000009.12 (120902393..120929173, complement) |
TRAF1 is a member of the TNF receptor (TNFR), associated with the factor family. It is responsible for the negative regulation of NFKB/TLR signaling. In addition, TRAF1 blocks oligomerization of TRAF6. In turn, TRAF1 plays a role in regulating signaling in various pathways that span from the immune system to cancer.
The best uses for the TRAF1 marker are for diagnosis of disease, drug discovery, and biomarker identification. The fusion gene binds TNF receptors and negatively regulates the Nod-like and Toll-like receptor signaling. It also sequesters a linear ubiquitin assembly compound. TRAF1 is a multi-functional protein in human disease. It is also found to be overexpressed in various types of B-cell cancers. TRAF1 has been linked to non-Hodkin's lymphoma through single nucleotide polymorphisms.
TRAF1 antibody was identified as A01365. A549 cells were stained with the antibody using an amount of normal goat serum. After incubation, the membrane could be examined using a goat anti-rabbit HRP secondary antibody in a 1:5000 dilution. The Tanon 5200 system used an Enhanced Chemiluminescent detection tool to create the signal. The 46KD band was within the normal TRAF1 size range.
TNF receptor-associated factors is encoded by the TRAF1 gene. Siemienski's team mapped the gene to 9q33-9q34. This gene is associated with LMP1 in vivo (TRAF3). LMP1 redirects EBI6 and LAP1 (TRAF3) to plasma membrane patches, where they interact with p80/TNFR2.
TRAF proteins with activation are essential for differentiation of immune cells. These ligated proteins activate CD40 by binding to their targets. The TRAF1 ligation of CD40 permits the transcription of a particular gene. Additionally, TRAF1 binds TRAF2 and TRAF3 to stimulate B cells. The mTRAF2/3 gene has a conserved TRAF6 binding motif, whereas murine CD40 contains an PxQxT motif and is proline-rich.
Transfection of HEK293 cell lines using Flag-TRAF1 or Myc-CK8 expression vectors results is a high level in RNAi activity. Anti-HA antibody detection of the polyubiquitinated form of TRAF6. Western blot analysis was performed using an anti-HA antibody. The results were then analyzed using an anti-CK8 antibody.
RelBDOLIGO mice are less likely to develop symptoms of disease and are immune-competent. They also develop anemia slower than wild-type mice and do not have high levels in IL-10. The severity of their disease was reduced by RelBDOLIGO mice, however their peak score was considerably lower. RelBDOLIGO mice had a lower percentage of diffuse inflammatory cells however, their severity was not affected. There was also a notable reduction in the number of immune cells that were infiltrating the brain, particularly CD4+ T cells.
Co-expression of EBER1 and LMP1 is linked to the development of osteosarcoma. The co-expression of these two genes in tumor cells is linked to worse outcomes for patients and a higher risk of malignancy. The study also found that both gene variants are extremely expressed in patients with bone sarcomas that are aggressive. There was no relationship between EBER1 coexpression and poor prognosis.
A genome-wide association study found that RA in humans was associated with the TRAF1–C5 locus. In this study 400 RA patients were examined for TRAF1 homozygosity. They found an increased risk of death from a variety of causes such as sepsis and malignancies. More research is required to confirm the results.
The TRAF1 marker plays a negative regulatory role in the NF-kB signaling. By limiting NF-kB during repeated exposures to innate immune stimuli, TRAF1 limits inflammatory responses in humans. It also hinders the survival of T cells that are stimulated by TNFR superfamily members. Even though a slightly lower TRAF1 level might not have a significant impact on human health in general, the consequences of chronically low TRAF1 levels aren't fully understood.
The TRAF1 marker has many functions in complex biological systems. It interacts with LUBAC and is a substrate in the LMP1 signaling pathway, as well as an inhibitor in the TLR pathway. TRAF1 binding and LUBAC binding aren't the only elements that can negatively regulate NFKB activation. These interactions are essential for understanding the mechanism behind TLR/NFKB signaling.
TRAF6 is also responsible for DC maturation. In mice, DCs that are deficient in TRAF6 lack the capacity to upregulate MHC and secrete IL-12 and IL-6 which are essential for DC maturation and immune tolerability. It is therefore possible that TRAF6-deficient DCs are defective in anti-apoptotic activity.
Studies on mice lacking TRAF1 demonstrate that these mice have increased responses to TLR signaling. It is possible that the skin damage caused by TNF could have led to an increase in TLR signaling through skin-associated microbes. TLRs could be responsible for the negative regulatory role mice with TRAF1 have. TRAF1 is a crucial component of lymphocyte survival, but it is also responsible for cell death.
TRAF1 is a nuclear receptor that stimulates the NF-kB system in response to inflammatory stimuli. It has many diverse roles in the nervous system that include learning, plasticity and memory. The NF-kB activators include growth factors, glutamate, and synaptic transmission. It is not known how TRAF1 affects TLR/NFKB signaling.
Previous studies have demonstrated that TRAF1- and ALK genes co-express in lymphoma. However, the role of PKN1 in this process is yet to be uncovered. While the exact mechanism of PKN1 is unknown however, evidence from cell lines indicates that TRAF1 enhances TRAF2-mediated signaling NSCLC. The TRAF1 gene is associated with several cancers including breast and lung cancer.
Although TRAF1 is abundantly expressed in CD8 T cells that respond to HIV, the protein's levels decrease as the severity of the infection increases. In HIV-specific CD8 T cells from chronic progressors and elite controllers, the level of TRAF1 is higher. TRAF1+ T cell were also associated with a lower proportion of high exhaustion PD-1 T cells.
Using a chimeric raphe nucleus approach, we have demonstrated that forced expression of TRAF1 marker CK8 significantly reduced the oligomerization of TRAF6. CK8 inhibits both K48 polyubiquitination and K63 polyubiquitination. This is believed to influence the signaling process in cells. We conclude that TRAF6 regulates the immune system and that forced expression of CK8 decreases the oligomerization process.
We used TLRs in order to activate a TLR in order to determine the function of CK8 within the innate response. TRAF6 activation activates an downstream signaling pathway that triggers the production proinflammatory Cytokines. CK8 downregulation enhances IL-1b as well as LPS signaling. CK8 is expressed by cells in response to fungal or bacteria infections. It has been proven that it negatively regulates the signaling of TLR/NFKB.
TRAF2 and cIAP1 are both able to activate NF-kB. They regulate the balance between pro-cell death as well as pro-activation. TRAF1 and TRAF2 are two signal transducers that recruit to the receptor complex. The c-IAPs regulate their functions. TRAF2-mediated NFKB, on other hand, is not affected by the c-IAPs.
We employed 293 cells that were transfected with various combinations of expression vectors. The cells were collected in the presence of phosphate buffered, saline/1mM Phen pelleted. Afterwards, we used lysis buffer with protease inhibitors and glutathione-Sepharose beads to precipitate the TRAF1 protein. This method was used to identify two genes that are involved in apoptosis, PDCD5 and TRAF2.
The TRIP gene interacts with TRAF1 and TRAF2 in yeast. TRAF1 fused proteins bind to TRIP. TRIP interacts with both GST alone and TRAF2 as an fusion protein. These interactions are crucial for understanding the role TRAF1 plays in cell development and function. What is the role of TRIP?
Transfection of HEK293 cells using the constructs indicated decreased oligomerization TRAF6. Immunoprecipitation using anti-HA antibodies has been used to detect polyubiquitinated TRAF6. Polyubiquitination of TRAF6 was confirmed by an immunoblot analysis of colons from CK8+ mice. Our results support the idea that CK8-mediated cell loss causes reduced TRAF6 levels in the colon.
PMID: 7859281 by Mosialos G., et al. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family.
PMID: 8069916 by Rothe M., et al. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.