Disease relevance of TRAP1

• When human leukemia HL60 cells and human lung cancer DMS114 cells were treated with beta-HIVS, the amount of TRAP1 in mitochondria decreased in a time-dependent manner during apoptosis [1].
• A second novel protein (EBI6), induced by EBV infection, is the human homolog of a second murine TNFR-associated protein (TRAF1) [2].
• Interestingly, those genes involved in NF-kappaB regulation, such as TNFR-associated factors 2 and 5 and B cell leukemia/lymphoma 10, were readily decreased upon STAT5, but not STAT3, depletion as validated by quantitative RT-PCR [3].
• The BT Trap is the first trap designed specifically for the detection and monitoring of mite infestation [4].
• Downregulation of TNF receptor-associated protein-2/p97 in renal cell carcinoma [5].

High impact information on TRAP1

• Recent research suggests that several TNF-R-associated proteins, including kinases, may initiate cytoplasmic signal transduction [6].
• Severe TNF receptor-associated periodic syndrome due to 2 TNFRSF1A mutations including a new F60V substitution [7].
• LMP1 has two C-terminal cytosolic domains, transformation effector sites (TES)1 and -2, that engage TNFR-associated factors (TRAFs) and the TNFR-associated death domain protein, respectively, and activate NF-kappaB [8].
• Cardiac glycosides inhibit TNF-alpha/NF-kappaB signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor [9].
• A possible mechanism for MYC-mediated apoptosis was revealed by identification of the tumor necrosis factor receptor associated protein TRAP1 as a MYC target [10].

Biological context of TRAP1

• Treatment of DMS114 cells with TRAP1-specific siRNA sensitized the cells to beta-HIVS-induced apoptosis [1].
• HSP90AA genes mapped onto chromosomes 1, 3, 4, and 11; HSP90AB genes mapped onto 3, 4, 6, 13 and 15; HSP90B genes mapped onto 1, 12, and 15; and the TRAP1 gene mapped onto 16 [11].
• Identification of TRAP-1 may be an important step toward defining how TNFR-1, which does not contain protein tyrosine kinase activity, transmits its message to signal transduction pathways [12].
• The 97-kDa TNFR-associated protein, TRAP2, shows sequence identity with internal amino acid sequences from subunit 2 of the 26S protease [13].
• Treatment of platelets with the blocking monoclonal antibody IV.3 against FcgammaRIIA, but not with control IgG, inhibited platelet aggregation induced by TRAP1, TRAP4, the thromboxane analogue U46619, and low concentrations of thrombin [14].

Anatomical context of TRAP1

• These results suggest that suppression of the expression of TRAP1 in mitochondria might play an important role in the induction of apoptosis caused via formation of ROS [1].
• TRAP-1 mRNA was also detected in each of eight different transformed cell lines [12].
• The 2.4-kilobase TRAP-1 mRNA was variably expressed in skeletal muscle, liver, heart, brain, kidney, pancreas, lung, and placenta [12].
• In this study, we examined the effect of DFO on tumor necrosis factor receptor-associated protein 1 (TRAP1), a representative mitochondrial HSP, in a normal human hepatocyte cell line, Chang cells [15].
• Iron chelation study in a normal human hepatocyte cell line suggests that tumor necrosis factor receptor-associated protein 1 (TRAP1) regulates production of reactive oxygen species [15].

Associations of TRAP1 with chemical compounds

• In addition, TRAP1 exhibited ATPase activity that was inhibited by both geldanamycin and radicicol [16].
• Involvement of tumor necrosis factor receptor-associated protein 1 (TRAP1) in apoptosis induced by beta-hydroxyisovalerylshikonin [1].
• The suppression of the level of TRAP1 by either beta-HIVS or VP16 was blocked by N-acetyl-cysteine, indicating the involvement of reactive oxygen species (ROS) in the regulation of the expression of TRAP1 [1].
• After in vitro transcription/translation and 35S labeling, TRAP-1 was precipitated using a fusion protein consisting of glutathione S-transferase and TNFR-1IC, showing that the two proteins directly interact [12].
• These effects were abrogated by hindrance of physical platelet-endothelial contacts using transwell systems or inhibited by GRGDSP, mAbs anti-GP IIb/IIIa (7E3), anti-alpha(v)beta3 (LM609), or anti-CD40L (TRAP1) [17].

Physical interactions of TRAP1

• The ability of deletion mutants of TNFR-1 to interact with TRAP-1 was tested using the two hybrid system [12].
• The inhibitory mutant has no TNFR-associated factor 2-binding capabilities and inhibits the recruitment of TNFR-associated factor 2 to the CD40 signaling complex after stimulation [18].

Regulatory relationships of TRAP1

• Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1 [19].
• Specifically, pro-inflammatory genes such as TNFalpha, IL-1beta, and MCP-1/MCAF-1 were down-regulated and anti-inflammatory genes such as TRAP1 and SMAD4 were induced [20].
• TICAM1 activates NF-kappaB through two different pathways involving its interactions with TNFR-associated factor 6 and receptor-interacting protein 1 [21].
• In Paracentrotus lividus embryos the inducible forms of HSP70 (HSP70/72) are different in molecular mass from the constitutively expressed HSP75, and they can be used as markers of cellular stress [22].

Other interactions of TRAP1

• Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease [13].
• Analysis of molecular mechanisms involved showed that it was not related to altered ex vivo expression of TNFR1-associated death domain, receptor interacting protein, or TNFR-associated factor 2 [23].
• Cooperation between TNF Receptor-Associated Factors 1 and 2 in CD40 Signaling [24].
• In this review, we summarize these and other TNF receptor-associated proteins and their potential roles in regulating the activation of nuclear factor-kappaB and apoptosis, two major responses activated by engagement of TNF receptors by the ligand [25].
• Microarray analysis of gene expression revealed that IL-10 activated various genes essential for macrophage functions, including other members of the TNFR superfamily, receptors for chemokines and growth factors, Toll-like receptors, and TNFR-associated signaling molecules [26].

Analytical, diagnostic and therapeutic context of TRAP1

• Immunofluorescence data show that human TRAP1 is localized to mitochondria [16].
• In this study, we performed cDNA array analysis and found that beta-HIVS suppressed the expression of the gene for tumor necrosis factor receptor-associated protein 1 (TRAP1), which is a member of the heat-shock family of proteins [1].
• Western blot analysis of purified rat liver mitochondrial subfractions with the TRAP-1 antibody reveals that the cross-reactive protein (M(r) approximately 80 kDa) is mainly present in the matrix compartment [27].
• We have used quantitative immunogold electron microscopy and biochemical analysis to evaluate the subcellular distribution of TRAP-1 in rat tissues [27].
• Immunoelectron microscopy provides evidence that tumor necrosis factor receptor-associated protein 1 (TRAP-1) is a mitochondrial protein which also localizes at specific extramitochondrial sites [27].

References