Within the tumor necrosis factor receptor (TNFR; see TNFR1 (OMIM 191190)) superfamily there is a subgroup termed death
receptors, which contain a cytoplasmic death domain. Activation of these receptors leads to the engagement of
components of the cell death pathway, including the adaptor molecule TRADD.
NCBI Summary:
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-kappaB and MAPK8/JNK, and induce cell apoptosis. Through its death domain, this receptor interacts with TRADD protein, which is known to serve as an adaptor that mediates signal transduction of TNF-receptors. Knockout studies in mice suggested that this gene plays a role in T-helper cell activation, and may be involved in inflammation and immune regulation.
General function
Receptor, Cell death/survival, Apoptosis
Comment
Cellular localization
Plasma membrane
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Ovarian function
Follicle atresia
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Bridgham JT, et al 2001 reported the conservation of death receptor-6 in avian and piscine
vertebrates.
The avian and piscine orthologs of DR6
have been identified, and the deduced amino acid sequence for each
demonstrates a high level of conservation compared to the mammalian sequence.
Expression of dr6 mRNA occurs widely across tissues of both the mature chicken
and brook trout. Of particular interest was the finding that elevated levels of
dr6 mRNA, as well as the translated protein, are expressed in atretic compared
to healthy follicles of the hen ovary, thus providing the first association
between DR6 expression and apoptosis, in vivo.
Expression regulated by
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Ovarian localization
Ovarian tumor
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Expression of death receptor 6 by ovarian tumors in laying hens, a preclinical model of spontaneous ovarian cancer. Barua A et al. Tumor-associated neoangiogenesis and suppression of antitumor immunity are hallmarks of tumor development and progression. Death receptor 6 (DR6) has been reported to be associated with suppression of antitumor immunity and tumor progression in several malignancies. However, expression of DR6 by malignant ovarian epithelial tumors at an early stage is unknown. The goals of this study were to determine whether DR6 is expressed by malignant ovarian epithelial tumors at an early stage and to examine whether DR6 expression is associated with ovarian cancer (OVCA) progression in a laying hen model of spontaneous OVCA. Expression of DR6 was examined in normal and malignant ovaries, normal ovarian surface epithelial (OSE) cells, or malignant epithelial cells and in serum of 3-year-old hens. The population of microvessels expressing DR6 was significantly higher in hens with early-stage OVCA than hens with normal ovaries (P < .01) and increased further in late-stage OVCA. The results of this study showed that, in addition to microvessels, tumor cells in the ovary also express DR6 with a significantly higher intensity than normal OSE cells. Similar patterns of DR6 expression were also observed by immunoblot analysis and gene expression studies. Furthermore, DR6 was also detected in the serum of hens. In conclusion, DR6 expression is associated with OVCA development and progression in laying hens. This study may be helpful to examine the feasibility of DR6 as a useful surrogate marker of OVCA, a target for antitumor immunotherapy and molecular imaging and thus provide a foundation for clinical studies.