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FAS (Fas Cell Surface Death Receptor, also known as apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6) is a Protein Coding gene, the most intensely studied member of the death receptor family. An important paralog of this gene is LTBR. The protein encoded by FAS gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Among those classical signal pathways, NF-κB has been identified as a critical promoter of cancer development, and directly regulates Fas transcription to modulate Fas-mediated apoptosis and tumor suppression. Engagement of Fas with FasL (ligand for FAS) triggered NF-κB activation. FAS is also a receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both.
Several alternatively spliced transcript variants of FAS have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. Researchers have identified and characterized three human mRNA Fas variants: FasTMDel, FasDel2, and FasDel3. The secreted isoforms 2 to 6 block apoptosis (in vitro). Immunocytochemical and in vitro apoptosis inhibition studies suggest that the transcripts are expressed as soluble Fas proteins that may play a functional role in the regulation of apoptosis.
It has been shown that FAS plays a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. Apoptosis triggered by Fas-FasL binding regulates the immune system. Its functions include T-cell homeostasis, cytotoxic T-cell activity, immune privilege, maternal tolerance, and tumor counterattack. Diseases associated with FAS include autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferative syndrome. During cancer progression FAS is frequently downregulated or cells are apoptosis resistant, raising the possibility that loss of FAS is part of a mechanism for tumour evasion, but in fact complete loss of FAS is rarely seen in human cancers. On the contrary, many cancer cells express large quantities of FAS and are highly sensitive to FAS mediated apoptosis in vitro. Furthermore, cancer patients frequently have elevated levels of the physiological FasL. The constitutive activity of FAS, stimulated by cancer-produced FasL, could actually promote the growth of tumours, for optimal growth, through its nonapoptotic activities. According to numerous experimental results, researchers demonstrate that FAS plays a growth promoting role during tumorigenesis and suggest that efforts to inhibit its activity rather than to enhance its activation should be considered during cancer therapy. Recently, FasL-mediated apoptosis of T cells has also been suggested as an immune-evasive mechanism by which tumors can suppress T cell infiltration similar to inhibitory immune checkpoints such as PD-1 and CTLA-4.
Apoptotic signaling via Fas/FasL (Akiko Yamada et al., 2017)
CRISPR/Cas9 PlatformCB, a global leading biotechnological company specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene editing services and products to a wide range of genomics researchers in the market. With deep gene editing knowledge and extensive experience in experimental operation and data processing, we can help you effectively control target genes deleted, inserted or point mutated in vivo and in vitro using CRISPR/Cas9 technology.
We have successfully implemented Fas CRISPR/Cas9 gene edited in >200 types cells including hard-to-transfect cells. To support your projects, we will offer you full-length custom Fas gene editing service from strategy design to final stable cells. Our Fas gene editing cell line generation services include:
➢ gRNA design and synthesis
➢ Transfect the cell lines you're interested
➢ Select the high expression cells and sort monoclonal cell
➢ Validate theknockout/knockin/point mutation of Fas by PCR and sequencing
➢ Produce cryogenic preserved vials of stable cells and a final report
Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc.
CRISPR/Cas9 PlatformCB also has extensive experience in incorporating CRISPR-Cas9 technology into animal models, which have been fully recognized by our clients. Tell us the gene name, we provide a one-stop-shop Fas CRISPR/Cas9 gene editing animal service and guarantee at least 2 founders or 3 F1 animals with shorter turnaround time and lower price. Our Fas gene editing animal model generation services include:
➢ Fas gene conventional knockout animals
➢ Fas gene conditional knockout animals
➢ Fas point mutation animals
➢ Fas knockin animals
Alternative species: mouse, rat, rabbit, zebrafish, C. elegans, etc.
CRISPR/Cas9 PlatformCB is devoted to providing the best gene editing services and products for academic research, biotech research and pharmaceutical drug discovery with excellent quality management and quality assurance capacity. To accelerate the achievement of your research goals, our gene editing expert team provides you with custom CRISPR/Cas9 services for any specific gene to help you solve problems encountered during your research. There is no doubt that CRISPR/Cas9 PlatformCB will be your best partner to support your research.
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