FASL

Official Full Name

Fas ligand

Organism

Homo sapiens

Gene ID

356

Background

This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]

Synonyms

FASLG; APTL; FASL; CD178; CD95L; ALPS1B; CD95-L; TNFSF6; TNLG1A; APT1LG1

Cat.No.	Product Name	Price
CSC-DC005539	Panoply™ Human FASLG Knockdown Stable Cell Line	Inquiry
CSC-SC005539	Panoply™ Human FASLG Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD06059Z	Human FASLG adenoviral particles	Inquiry

Cat.No.	Product Name	Price
SHH049493	shRNA set against Rat Faslg(NM_012908.1)	Inquiry
SHH049511	shRNA set against Human FASLG(NM_000639.1)	Inquiry
SHH292485	shRNA set against Human Fasl (NM_000639.1)	Inquiry
SHH292489	shRNA set against Mouse Fasl (NM_010177.4)	Inquiry
SHH292493	shRNA set against Rat Fasl (NM_012908.1)	Inquiry
SHW002143	shRNA set against Chicken FASLG (NM_001031559)	Inquiry
SHW009711	shRNA set against Danio rerio FASLG (NM_001042701)	Inquiry

Cat.No.	Product Name	Price
CDFH006614	Human FASLG cDNA Clone(NM_000639.1)	Inquiry
CDFH006615	Human FASLG cDNA Clone(NM_000639.1)	Inquiry
CDFR010618	Rat Faslg cDNA Clone(NM_012908.1)	Inquiry
MiUTR1R-01828	FASLG miRNA 3'UTR clone	Inquiry
MiUTR3H-00783	FASLG miRNA 3'UTR clone	Inquiry
CDCB159575	Human FASLG ORF clone (BC017502)	Inquiry
CDCB163618	Chicken FASLG ORF Clone (NM_001031559)	Inquiry
CDCB171186	Danio rerio FASLG ORF Clone (NM_001042701)	Inquiry
CDCB191284	Rabbit FASLG ORF clone (XM_008263787.1)	Inquiry
CDCL184183	Human FasL ORF clone(NM_000639.1)	Inquiry
CDCL184184	Mouse FASL ORF clone(NM_010177.4)	Inquiry
CDCL184185	Rat FasL ORF clone(NM_012908.1)	Inquiry
CDCR063886	Mouse Fasl ORF clone (NM_001205243.1)	Inquiry
CDCS405812	Human FASLG ORF Clone (BC017502)	Inquiry

Detailed Information

Fasl, also known as CD178, is a type II transmembrane glycoprotein, a member of the tumor necrosis factor ligand superfamily, and it can specifically bind to Fas. Both human and mouse Fasl genes are located in chromosome No. 1 and contain 5 exons. Fasl is a homotrimer, with membrane-bound Fasl, soluble Fasl and microtubule-associated Fasl. Both membrane-bound Fasl and soluble Fasl bind to Fas on target cells in the form of trimers, induce Fas to form trimers, and mediate cell apoptosis.

Fas/Fasl System and Apoptosis

In the process of apoptosis signal transduction mediated by the Fas /Fasl system, Fas must be oligomerized to form a trimer, thereby transferring the extracellular death signal into the cell. After Fasl or a competitive antibody binds to its corresponding death receptor, the Fas cytoplasmic region is post-transcriptionally modified to induce the repressor domain of the Fas cytoplasmic segment to separate from Fas-binding phosphatase 1. At the same time, it induces the death domains in the Fas molecule to aggregate with each other to form trimers and recruit to lipid rafts. The death domain of the trimer combines with the death domain of the Fas-associated death domain (FADD) to form a death-inducing signal complex. The other end of the FADD molecule contains a death effect domain that can bind to procapase -8 / -10. Procapase-8/-10 also contains a death effector domain. The two can interact with the homologous protein domain to form a death-inducing signal complex composed of Fas/FADD/procaspase-8/-10. Caspase is considered to be an apoptotic effector enzyme. The accumulation of procapase in the apoptotic enzyme body leads to self-hydrolysis and activation, forming active caspase-8/-10. The latter can activate other zymogens in its homologous enzyme family, such as its downstream procaspase-3 /-6 /-7).

Figure 1. Proinflammatory feed-forward loop between lipotoxic hepatocytes and activated macrophages. (Hirsova, P., et al. 2015)

Fasl and Tumor

In recent years, studies have found that testicular stromal cells, cornea, iris, and retinal cells continue to express Fasl. Activated lymphocytes enter these tissues and interact with Fasl and undergo apoptosis. Fas expression on the surface of many tumor cells is reduced or even not expressed. Because Fas receptors are actively reduced, tumor cells are less sensitive to Fasl-positive TILs, so tumor cell apoptosis cannot be initiated. The expression of Fas and Fasl in tumor tissues is diverse. Some tumor cells express both Fas and Fasl, but do not undergo apoptosis after contact with TILs. In chronic myelogenous leukemia (CML), the expression level of Fas on tumor cells is higher, but it is not sensitive to Fasl expressed by lymphocytes, which prevents tumor cell apoptosis.

CML's tumor cell generation period is prolonged and the treatment effect is poor. The genotype of Fas tested has been mutated. Similarly, colon cancer and lung cancer tissues can also use Fas mutations to change the pathway of Fas initiating apoptosis signals or interfere with the conduction of apoptosis signals, and reduce the sensitivity of tumor cells Fas to T cells Fasl. For example, the binding of SFas and Fas1 can competitively inhibit the binding of membrane Fas and Fasl, so that tumor cells can resist Fas-mediated apoptosis. Although cancer cells have Fas receptors and can bind to activated T cells Fasl, they cannot initiate apoptosis.

References:

Hirsova, P., & Gores, G. J. (2015). Death Receptor-Mediated Cell Death and Proinflammatory Signaling in Nonalcoholic Steatohepatitis. Cellular and molecular gastroenterology and hepatology, 1(1), 17-27.
Rossin, A., Miloro, G., & Hueber, A. O. (2019). TRAIL and Fasl Functions in Cancer and Autoimmune Diseases: Towards an Increasing Complexity. Cancers, 11(5), 639.
Wang, M., & Su, P. (2018). The role of the Fas/Fasl signaling pathway in environmental toxicant-induced testicular cell apoptosis: An update. Systems biology in reproductive medicine, 64(2), 93–102. https://doi.org/10.1080/19396368.2017.1422046.

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