Disease relevance of DAP3

• In glioma cell lines T98G and G112 with an induced motility phenotype, Dap-3 was up-regulated at the mRNA and protein level as assessed by quantitative reverse transcription-PCR, cDNA microarray, and Western blot analysis [1].
• CONCLUSIONS: Dap-3 is up-regulated in invasive glioblastoma multiforme cells in vivo and in glioma cells with an induced motility phenotype in vitro [1].
• Mutational analysis of proapoptotic death associated protein 3 (DAP3) P-loop domain in common human carcinomas [2].

High impact information on DAP3

• Interaction of DAP3 and FADD only after cellular disruption [3].
• We have found that the GTP-binding protein DAP3 binds directly (with high affinity) to the death domain of TNF-related apoptosis-inducing ligand (TRAIL) receptors, and is required for TRAIL-induced apoptosis [4].
• Expression of anti-sense DAP3 RNA and of the dominant interfering form of DAP3 both protected cells from apoptosis induced by activation of Fas and tumor necrosis factor alpha (TNF-alpha) receptors [5].
• We also showed that DAP3 is phosphorylated by kinase Akt (PKB), and active Akt can nullify apoptosis induction by DAP3 [6].
• Conversely, overexpression of DAP3 augmented cell death and caspase activation induced by cell detachment [6].

Biological context of DAP3

• TRAIL-induced apoptosis is independent of the mitochondrial apoptosis mediator DAP3 [7].
• Involvement of DAP3 in anoikis signaling demonstrates a novel role for this GTP-binding protein in apoptosis induction caused by cell detachment [6].
• Mutation of a consensus Akt phosphorylation site in DAP3 renders it resistant to suppression by active Akt in cells [6].
• Down-regulation of DAP3 expression by antisense oligonucleotides inhibited anoikis [6].
• Although the levels of pro-Caspase-8 appeared sufficient, inadequate levels of Fas-associated death domain protein (FADD) and DAP3 may preclude assembly of the death-inducing signaling complex [8].

Anatomical context of DAP3

• To address these discrepancies, the intracellular localization of DAP3 after apoptosis induction in human T-lymphocytes with recombinant TRAIL was analyzed [7].
• TRAIL-induced and DR4-mediated apoptosis in Jurkat cells is independent of DAP3 [7].
• Recent reports have suggested that DAP3 is localized to the mitochondria, but no functional significance of this localization has been reported so far [9].
• Ectopic expression of DAP3 in HeLa cells was not compatible with cell growth, resulting in a 16-fold reduction in the number of drug-resistant stable clones [10].
• The Death Associated Protein 3 (DAP3), a GTP-binding constituent of the small subunit of the mitochondrial ribosome, is implicated in the TNFalpha and IFNgamma apoptotic pathways of the cell and is involved in the maintenance of the mitochondrial network [11].

Associations of DAP3 with chemical compounds

• Integrin ligation stimulates Akt activation and phosphorylation of DAP3 in intact cells, as well as suppresses the ability of DAP3 overexpression to augment anoikis [6].
• Co-transfection experiments in COS-7 cells showed that DAP3 had a stimulatory effect on the ligand-induced transcriptional activation by GR and also increased the steroid-sensitivity [12].
• DAP3 has motifs characteristic of guanine nucleotide binding proteins and is probably the protein that accounts for the nucleotide binding activity of mammalian mitochondrial ribosomes [13].
• These are Arg tyrosine kinase and death-associated protein 3 (DAP3), which are known as ionizing radiation resistance conferring proteins [14].

Physical interactions of DAP3

• In vitro experiments showed that the full-length DAP3 also interacted with GR [12].

Other interactions of DAP3

• Therefore, DAP3 and FADD interact only in vitro after disruption of the cellular compartments [7].
• Functional interaction between the pro-apoptotic DAP3 and the glucocorticoid receptor [15].
• Structure-function analysis of an evolutionary conserved protein, DAP3, which mediates TNF-alpha- and Fas-induced cell death [5].
• Proteolytic digestion of whole mitochondrial ribosomal subunits followed by analysis of the peptides present using liquid chromatography-tandem mass spectrometry revealed that the proapoptotic proteins, death-associated protein 3 (DAP3) and the programmed cell death protein 9, are both components of the mitochondrial ribosome [13].
• DAP3 was expressed in normal bronchial epithelial cells, and the expression was induced by IFN-gamma [16].

Analytical, diagnostic and therapeutic context of DAP3

• No interaction between FADD and DAP3 after cell fractionation could be detected as long as subcellular compartments remained intact [7].
• Only whole cell lysate co-immunoprecipitation revealed an ex vivo interaction between DAP3 and FADD [7].
• To assess the possible involvement of genetic variants of DAP3 with asthma, we searched for single-nucleotide polymorphisms (SNPs) in the gene and conducted a case-control study with 1,341 subjects [16].
• In Northern blots, an induction was confirmed for the new gene, DAP3 and PTZ-17 were down-regulated in some but not in all parallel experiments; however, basal level of H-NUC mRNA was too low to be detected in Northern blots [17].
• Assignment of death associated protein 3 (DAP3) to human chromosome 1q21 by in situ hybridization [18].

References