Disease relevance of TNFRSF6

• So far, the presence of Fas antigen in ejaculated spermatozoa was related only to subfertility or infertility conditions [1].
• Bovine herpesvirus 4 BORFE2 protein inhibits Fas- and tumor necrosis factor receptor 1-induced apoptosis and contains death effector domains shared with other gamma-2 herpesviruses [2].

High impact information on TNFRSF6

• Fas antigen (Fas Ag; CD95) is a cell surface molecule that can mediate apoptosis [3].
• Theileria parva-transformed T cells show enhanced resistance to Fas/Fas ligand-induced apoptosis [4].
• We observed upregulation of Fas in beta-cells of type 2 diabetic patients relative to nondiabetic control subjects [5].
• These results support a new role for glucose in regulating Fas expression in human beta-cells [5].
• These findings support the concept that CD4(+) CTL lyse macrophages pulsed with BHV-1 polypeptides through a Fas-mediated lytic pathway by inducing apoptosis in the target cells [6].

Biological context of TNFRSF6

• Both activation of the Fas pathway and presence of FSH during in vitro maturation increased the incidence of apoptosis in cumulus cells, affecting predominantly the middle and peripheral regions of the cumulus [7].
• Expression of components of the Fas signaling pathway was studied in both oocytes and cumulus cells by polymerase chain reaction after reverse transcription, immunoblotting, and indirect immunofluorescence [7].
• In an effort to characterize the possible role of Fas-mediated apoptosis in some important physiological processes in livestock, bovine Fas (bFas) cDNA was isolated and its nucleotide sequence determined [8].
• This system in the testis is believed to be a paracrine signaling system by which Sertoli cells expressing Fas L can initiate killing of Fas-expressing germ cells during spermatogenesis [1].
• These results provide a basis for further studies using the bovine ovary to examine the role of the Fas antigen in follicular atresia [9].

Anatomical context of TNFRSF6

• Fas mRNA and protein were expressed both in oocytes and cumulus cells [7].
• We demonstrated for the first time that normal ejaculated spermatozoa also express Fas antigen [1].
• Expression and function of Fas antigen vary in bovine granulosa and theca cells during ovarian follicular development and atresia [10].
• Regulation of Fas antigen (Fas, CD95)-mediated apoptosis of bovine granulosa cells by serum and growth factors [11].
• Expression and activity of the Fas antigen in bovine ovarian follicle cells [9].

Associations of TNFRSF6 with chemical compounds

• However, a gap exists in our understanding of the Fas-mediated signaling mechanisms that are involved in either the loss of progesterone production or the structural regression of the corpus luteum [12].
• Fas antigen mRNA was detectable in cultured granulosa and theca cells, and expression was increased by treatment with IFN but not TNF [9].
• Theca cells were sensitive to Fas-mediated apoptosis before and after exposure to the LH surge [13].
• These clustered LRs contained high NADPH oxidase activity, which increased in response to Fas stimulation [14].
• Treatment with anisomycin or daunorubicin in the presence of ZVAD increased expression of FasL mRNA and protein but did not alter expression of Fas mRNA or protein [15].

Physical interactions of TNFRSF6

• Fas antigen is a receptor that triggers apoptosis when bound by Fas ligand (FasL) [10].

Regulatory relationships of TNFRSF6

• IFN increased expression of Fas similarly in all types of media but was required for FasL-induced killing only in BM containing FBS or IGF [11].

Other interactions of TNFRSF6

• In isolated LR fractions from Fas-stimulated endothelial cells, gp91phox, p47phox (a crucial cytosolic regulatory subunit of NADPH oxidase), and Rac GTPase were markedly increased and blocked by nystatin, a compound that disrupts LRs [14].

Analytical, diagnostic and therapeutic context of TNFRSF6

• FasL and Fas transcripts were analyzed by RT-PCR [16].
• We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection [17].
• FasL and Fas proteins were detected by flow cytometry and Western blot [16].
• After thawing, DNA fragmentation of surviving embryos was examined by TUNEL assay, and the expression patterns of their apoptotic genes (survivin, Fas, Hsp 70 and caspase-3) were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction [18].
• When a coculture model is used in which infected and uninfected cell populations were physically separated by a semipermeable membrane, both uninfected biliary epithelia and uninfected Fas-sensitive Jurkat cells (but not a Fas-resistant Jurkat cell line) underwent apoptosis when cocultured with infected biliary epithelia [19].

References