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Mulibrey Nanism
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
As a zinc finger protein in the tripartite motif (TRIM) protein family, TRIM37 comprises an N-terminal RING finger domain (a cysteine-rich, zinc-binding domain), a B-box motif (another cysteine-rich, zinc-binding domain), two coiled-coil regions, a central TNF-receptor-associated factor (TRAF)-like domain, a third coiled-coil domain, an acidic domain, two nuclear localization signals, and a second acidic domain. The RING finger and B-box domains chelate zinc and participate in protein−protein and/or protein−nucleic acid interactions The TRAF-like domain interacts with TRAF and other proteins, and acts as scaffold molecules for receptors, kinases, and various regulators in signaling pathways [1].
Pathogenesis: Molecular mechanisms of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Anastasia E. Markatseli, Theodora E. Markatseli, Alexandros A. Drosos
The Fc receptor common γ subunit (FcRγ) and DNAX-activating protein 12 (DAP12) constitute a signaling system that participates in the differentiation of osteoclasts. This system alone is not capable of increasing the transcription of NFATc1 and inducing the formation of osteoclasts. Therefore, it cooperates with the pathway induced by the binding of RANK to TRAF 6 (172). OPG binds to RANKL and inhibits its activity, blocking the interaction of RANKL with RANK and therefore osteoclastogenesis.
M cells and the follicle-associated epithelium
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Hiroshi Ohno, Marian Neutra, Ifor R. Williams
The cytokine signals and intracellular signaling pathways that control enterocyte differentiation into M cells are beginning to be elucidated, particularly using enteroids. The addition of receptor activator of nuclear factor kappa B ligand (RANKL) to mouse enteroids rapidly increases the expression of M cell–associated transcripts such as Sp1B and CCL9; the effect is enhanced if TNF-α is added along with RANKL. Similar results occur when RANKL is added to monolayers of human small intestinal crypts. When RANKL binds to RANK, a signaling pathway is initiated via TNF receptor associated factor (TRAF6). Gut epithelial knockout of TRAF6 in mice completely abolishes the formation of M cells in FAE.
Asiaticoside reverses M2 phenotype macrophage polarization-evoked osteosarcoma cell malignant behaviour by TRAF6/NF-κB inhibition
Published in Pharmaceutical Biology, 2022
Tumour necrosis factor receptor-associated factor 6 (TRAF6) belongs to the tumour necrosis factor receptor-associated factor (TRAF) protein family and is critical for regulating toll-like receptor (TLR)-mediated signalling (Akira et al. 2001). TRAF6 is located at the centre of signal aggregation induced by toll-like receptor and tumour necrosis factor receptor families and is widely interrelated to inflammatory and immune responses mainly through mediating inflammatory and apoptotic signalling pathways (Inoue et al. 2007). TRAF6 binds to NF-κB-induced kinase and other signalling molecules and is the critical activator of the NF-κB signalling pathway (Ye et al. 2002). TRAF6 exerts pivotal functions in tumorigenesis mainly by the regulation of the NF-κB signalling pathway. For instance, colorectal cancer patients with high expression of TRAF6 have poor survival, and TRAF6 further aggravates colorectal cancer by activating the TRAF6/NF-κB signalling pathway (Zhu et al. 2019); GTPase M accelerates the M2 phenotype macrophage polarization in gliomas through the TRAF6/NF-κB pathway, thereby accelerating the gliomas progression (Xu et al. 2019). Similar to the above conclusions, this research confirmed that ATS decreased the protein levels of TRAF6, and reduced the TRAF6/NF-κB activity in osteosarcoma cells, prompting that ATS might have a protective function in osteosarcoma through the inactivation of the TRAF6/NF-κB signalling pathway.
Circ_0114427 promotes LPS-induced septic acute kidney injury by modulating miR-495-3p/TRAF6 through the NF-κB pathway
Published in Autoimmunity, 2022
Lei Xu, Hongxia Cao, Peng Xu, Mingxi Nie, Chun Zhao
In addition, TRAF6, a downstream gene of miR-495-3p, was obviously upregulated in the serums of septic AKI patients and LPS-induced HK-2 cells in vitro. In the present study, TRAF6 was closely linked to the progression of cancer, specially, the expression of TRAF6 was notably increased and promoted colon cancer cell proliferation [42]. Besides, TRAF6 was also considered as a key regulator in adaptive immunity and innate immunity [43], and was referred to NF-κB/p65 signalling pathway [44,45]. Past researches have revealed that TRAF6 was a promoted oncogene bridged signalling pathways between RAS and NF-κB in human lung cancer [46]. What’s more, NF-κB pathway was also involved in inflammatory response [47]. Thus, we paid attention to the role of TRAF6 and relative NF-κB signalling pathway in AKI. Firstly, the expression of TRAF6 was enriched in LPS-induced HK-2 cells compared with no treated cells. Furthermore, the expression of NF-κB signalling pathway related proteins p-IκBα, t-IκBα, p-p65 and t-p65 was also measured in vitro. Furthermore, the facilitating effect of miR-495-3p on cell viability and inhibitory action of miR-495-3p in cell apoptosis and inflammatory response were restored by TRAF6 overexpression. Moreover, the suppressive effects of circ_0114427 knockdown on the expression levels of TRAF6, p-IκBα and p-p65 were all relieved by miR-495-3p silence. Thus, we speculated that circ_0114427 might participate in the progression of AKI by regulating miR-495-3p/TRAF6/NF-κB/p65 signalling pathway.
TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer
Published in OncoImmunology, 2018
Alexandre Ivagnès, Meriem Messaoudene, Gautier Stoll, Bertrand Routy, Aurélie Fluckiger, Takahiro Yamazaki, Kristina Iribarren, Connie P. M. Duong, Laetitia Fend, Anne Caignard, Isabelle Cremer, Axel LeCesne, Julien Adam, Charles Honoré, Olivier Mir, Loïc Chaigneau, Anne Berger, Pierre Validire, Christos Christidis, Valérie Le Brun-Ly, Mark J. Smyth, Xavier Mariette, Benoît L. Salomon, Guido Kroemer, Sylvie Rusakiewicz, Laurence Zitvogel
Tumor necrosis factor (TNF) receptor-associated factor (TRAF) 1 was originally identified based on its ability to interact with the cytosolic domain of TNF receptor type 2 (TNFR2).36 TRAF1 in fact associates with multiple TNFR family members and can also bind several protein kinases and adaptor proteins suggesting that TRAF1 likely possesses multiple functions in cytokine signaling networks. TRAF1 is unique among TRAF proteins for two reasons. First, it lacks a RING finger domain present in TRAF2-6 that has been shown to be required for TRAF2- and TRAF6-mediated activities. Second, TRAF1 has the most restricted expression among TRAFs, and is found almost exclusively in activated lymphocytes, dendritic cells, and certain epithelia.