Disease relevance of TRAF4

• Ductal carcinoma in situ (DCIS) lesions were uniformly TRAF-4 immunonegative (n = 21) [1].
• Basal cells in prostate hypertrophy (n = 6) and prostatic intraepithelial neoplasia (PIN; n = 6) were strongly TRAF-4 positive, but none of the 32 primary and 16 metastatic prostate cancer specimens examined contained TRAF-4-positive malignant cells [1].
• CART1 is specifically expressed by epithelial cells in breast carcinomas and metastases [2].
• Re: Pavelka K, Gatterova J, Gallerova V, Urbanova Z, Sedlackova M, Altman R. A 5-year randomized controlled double-bling study of glycosaminoglycan polysulfuric acid complex (Rumalon) as a structure-modifying therapy in osteoarthritis of the hip and knee. Oseoarthritis Cart 2000;8:335-342 [3].
• Oxygen consumption was measured simultaneously by the reverse Fick-principle (V02FICK) and by indirect calorimetry ("Metabolic Measurement Cart Horizon") (V02MMC) in 31 critically ill patients; 24 men and 7 women [4].
• To investigate changes in TRAF4 gene copy number, 125 cases from six different types of carcinomas were also analysed by fluorescence in situ hybridization [5].

High impact information on TRAF4

• TRAF4 directly associated with the focal contact scaffold Hic-5, and the knockdown of either protein, disruption of the complex, or oxidant scavenging blocked cell migration [6].
• We found that the nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase adaptor p47(phox) and its binding partner TRAF4 were sequestered within nascent, focal complexlike structures in the lamellae of motile endothelial cells [6].
• Our data suggest that TRAF4 specifies a molecular address within focal complexes that is targeted for oxidative modification during cell migration [6].
• Altogether, our results demonstrate that TRAF4 is required during embryogenesis in key biological processes including the formation of the trachea, the development of the axial skeleton, and the closure of the neural tube [7].
• Overexpression of proapoptotic proteins caspase-9 and TRAF4 was seen in endothelial cells and smooth muscle cells from unstable hemorrhagic and ulcerated plaque regions [8].

Biological context of TRAF4

• Furthermore, overexpression of TRAF4 abrogated the ability of dimerization to prevent the induction of apoptosis normally mediated by monomeric p75(NTR) [9].
• In addition to its role in p70S6K activation, we postulate an anti-apoptotic role for TRAF4, because the agonistic anti-Fas antibody CH-11 induced apoptosis in untransfected HEK-293 cells, but not in TRAF4-expressing HEK-293 cells [10].
• TRAF4 localizes to the cytoplasm and appears to remain in the cytoplasm following DNA damage [11].
• These data suggest that activation of the NF-kappaB pathway is involved in up-regulation of TRAF4 in T-cells [12].
• While TRAF4-GFP (T4-GFP) was clearly localized in the cytoplasm, the N-terminal deletion mutant, T4(259-470), comprising the TRAF domain of the molecule, and a C-terminal deletion mutant consisting mainly of the RING and zinc finger domains of TRAF4 were both localized predominantly to the nucleus [12].

Anatomical context of TRAF4

• A secondary screen of endothelial cell proteins for TRAF4-interacting partners yielded a number of proteins known to control cell fate [13].
• In addition, TRAF4, like p47(phox), was recovered largely in the cytoskeleton/membrane fraction [13].
• All three HD cell lines showed strong expression of TRAF2 protein and moderate, comparatively equal expression of TRAF4 and TRAF6 [14].
• Here, we show that endogenous TRAF4 and MEKK4 associate in both human K562 cells and mouse E10.5 embryos [15].
• These results suggest that TRAF4 participates in the molecular mechanism underlying silencing of TLR-mediated signaling through the interaction with molecules harboring phagosome/endosome membrane [16].

Associations of TRAF4 with chemical compounds

• The murine TRAF4 promoter contains a functional p53 DNA-binding site approximately 1 kilobase upstream of the initiating methionine [11].
• Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development [17].
• To validate two new commercial instruments, (Siemens-Elema Servo Ventilator 900B, Beckman Metabolic Cart), the authors constructed a lung model into which they delivered CO2 and N2 at precise rates to simulate Co2 production (Vco2) and O2 consumption (Vos) [18].
• On-line oxygen consumption VO2 measurements were obtained throughout using the Beckman Horizon Metabolic Cart [19].
• The nonintervened reference coronary segments of the PCI vessel demonstrated improvements with AGI-1067 in the Canadian Antioxidant Restenosis Trial-1 (CART-1), evidence supportive of a clinical effect on slowing atherosclerosis progression [20].

Physical interactions of TRAF4

• Immunoprecipitation experiments showed that stimulation of receptors of the tumor necrosis factor (TNF) family induced the formation of TRAF4/p70S6K complexes [10].

Regulatory relationships of TRAF4

• Despite intensive research, the function of TRAF4 in signaling pathways triggered by TNFR-related proteins remains enigmatic [21].

Other interactions of TRAF4

• Domain analysis suggested a tail-to-tail interaction between the C terminus of p47(phox) and the conserved TRAF domain of TRAF4 [13].
• Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase [13].
• TRAF4 functions as an intermediate of GITR-induced NF-kappaB activation [21].
• The isolated peptides have high sequence similarity with proteins such as TRAF4-associated factor 1, G protein-coupled receptor MRGX3, tumor necrosis factor superfamily (member 9), and c-Jun N-terminal kinase 3 [22].

Analytical, diagnostic and therapeutic context of TRAF4

• Immunofluorescence analysis of TRAF-4 in transfected cells demonstrated localization to cytosol but not nucleus [1].
• To test the inter-TriTrac reliability, two TriTrac-R3D accelerometers were worn during each exercise period, and to examine validity, a simultaneous measurement of energy expenditure was made using indirect calorimetry (SensorMedics 2900 Metabolic Cart) [23].
• Whenever possible, on-line computerized respiratory analysis (Beckman Metabolic Measurement Cart) was carried out during the exercise tests [24].
• Fluorescence in situ hybridisation (FISH) further identified the presence of human male X and Y chromosomes at engrafted sites, whilst the human origin of the cells was confirmed by a specific PCR assay for the human Cart-1 gene [25].
• INTERVENTION: Indirect calorimetry reports generated by the National Institutes of Health Critical Care Medicine Department's Metabolic Cart Consult Service were reviewed [26].

References