Chung, J. Y., Park, Y. C., Ye, H. & Wu, H. All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J. Cell Sci. 115, 679-688

Department of Biochemistry, Cornell University, Итак, New York, United States
Journal of Cell Science (Impact Factor: 5.43). 03/2002; 115(Pt 4):679-88.
Source: PubMed


The tumor necrosis factor (TNF) receptor associated factors (TRAFs) have emerged as the major signal transducers for the TNF receptor superfamily and the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily. TRAFs collectively play important functions in both adaptive and innate immunity. Recent functional and structural studies have revealed the individuality of each of the mammalian TRAFs and advanced our understanding of the underlying molecular mechanisms. Here, we examine this functional divergence among TRAFs from a perspective of both upstream and downstream TRAF signal transduction pathways and of signaling-dependent regulation of TRAF trafficking. We raise additional questions and propose hypotheses regarding the molecular basis of TRAF signaling specificity.

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    • "IRE1α plays a critical role in transcription of inflammatory genes due to its interaction with TRAF2, which promotes NF-κB activation and inflammatory response. The TRAF family proteins are intracellular adaptors that have been extensively studied in the signaling pathways of TNFR or IL-1/TLR super-families (Chung et al., 2002; Oganesyan et al., 2006; Bishop et al., 2007). All TRAF family proteins (TRAF1-7) have the most conserved TRAF domains in their carboxyl terminal region, which involve in binding to different receptor cytoplasmic tails and the formation of homo- or hetero-dimers between the family members. "
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    ABSTRACT: As an adaptive response to the overloading with misfolded proteins in the endoplasmic reticulum (ER), ER stress plays critical roles in maintaining protein homeostasis in the secretory pathway to avoid damage to the host. Such a conserved mechanism is accomplished through three well-orchestrated pathways known collectively as unfolded protein response (UPR). Persistent and pathological ER stress has been implicated in a variety of diseases in metabolic, inflammatory, and malignant conditions. Furthermore, ER stress is directly linked with inflammation through UPR pathways, which modulate transcriptional programs to induce the expression of inflammatory genes. Importantly, the inflammation induced by ER stress is directly responsible for the pathogenesis of metabolic and inflammatory diseases. In this review, we will discuss the potential signaling pathways connecting ER stress with inflammation. We will also depict the interplay between ER stress and inflammation in the pathogenesis of hepatic steatosis, inflammatory bowel diseases and colitis-associated colon cancer.
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    • "TNF receptor-associated factors (TRAF) play a major role in linking the TNF receptor to downstream signaling pathways [23]. However, TRAF2 has also been reported to be essential for PKC-dependent NF-κB signaling and JNK activation [24], [25], [26], [27]. "
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    Full-text · Article · Feb 2014 · PLoS ONE
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    • "TRAFs collectively play important roles, including actions in adaptive and innate immunity, embryonic development, the stress response and bone metabolism. These functions are mediated by TRAFs through the induction of cell survival, proliferation, differentiation and death (3–8). "
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    ABSTRACT: Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) was initially identified as a gene amplified and overexpressed in breast carcinoma. The present study investigated the expression and anti-apoptotic function of TRAF4 in human breast cancer MCF-7 cells. TRAF4 was found to be localized in the cytoplasm and nuclei of MCF-7 cells by immunofluorescence staining and western blotting. The expression of TRAF4 in normal MCF-10A breast cells was found to be lower than in MCF-7 and MDA-MB-231 breast cancer cells. Following TNF-α treatment, TRAF4 depletion by siRNA in the MCF-7 cells was observed to suppress cell proliferation and the nuclear expression of nuclear factor κB was significantly reduced. The percentage of early apoptotic cells in the MCF-7 cells was augmented upon TRAF4-knockdown, and an increase in G1 phase cells and a decrease in S phase cells was detected. These results indicate that TRAF4 has anti-apoptotic effects on apoptosis induced by TNF-α in MCF-7 cells.
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