FAS

Case study 1: Laurent Gagnoux-Palacios, 2018

Finely tuned regulation of epithelial cell death maintains tissue integrity and homeostasis. At the cellular level, life and death decisions are controlled by environmental stimuli such as the activation of death receptors. We show that cell polarity and adherens junction formation prevent proapoptotic signals emanating from the Fas death receptor. Fas is sequestered in E-cadherin actin-based adhesion structures that are less able to induce downstream apoptosis signaling. Using a proteomic-based approach, we find that the polarity molecule Dlg1 interacts with the C-terminal PDZ-binding site in Fas and that this interaction decreases formation of the death-inducing complex upon engagement with Fas ligand (FasL), thus acting as an additional cell death protection mechanism. Thus E-cadherin and Dlg1 inhibit FasL-induced cell death by two complementary but partially independent mechanisms that help to maintain epithelial homeostasis by protecting normal polarized epithelia from apoptosis. When polarity is lost, the Fas-cadherin-Dlg1 antiapoptotic complex is disrupted, and FasL can promote the elimination of compromised nonpolarized cells.

Fig1. Fas detergent solubility in HCT15 cells transfected by the indicated siRNAs was analyzed by IB.

Fig2. Accumulation of Fas and activated caspase-8 under FasL-coated beads was quantified.

Case study 2: María Florencia Sánchez, 2018

The cytotoxic synapse formed between cytotoxic T lymphocytes or natural killer cells expressing CD95L and target cells with CD95 on their surface is a key pathway for apoptosis induction by the immune system. Despite similarities with the immune synapse in antigen presenting cells, little is known about the role of the spatiotemporal organization of agonistic proteins/receptor interactions for CD95 signaling. Here, the researchers have developed an artificial cytotoxic synapse to examine how mobility and geometry of an anti-CD95 agonistic antibody affect receptor aggregation and mobility.

By measuring the distribution, diffusion coefficient, and fraction of immobile CD95 receptor in living cells, we show that at short times, the initial activation of CD95 occurs locally and is limited to the contact region of the cytotoxic synapse. This anisotropic activation of apoptotic signaling supports a role for confined interactions on the efficiency of signal transduction that may have implications for biomedical applications of extrinsic apoptosis induction.

Fig3. Effector Caspases 3/7 activity measured by luminescence in CD95 ko T98G cells.

Fig4. Diffusion coefficients of CD95 as obtained by FCS.

Fig1. Extrinsic and intrinsic apoptotic pathways. (Jean-Philippe Guégan, 2018)

Fig2. Fas-FasL interactions mediate immune cell homeostasis. (R M Siegel, 2000)

FAS involved in several pathways and played different roles in them. We selected most pathways FAS participated on our site, such as MAPK signaling pathway, Cytokine-cytokine receptor interaction, p signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with FAS were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

FAS has several biochemical functions, for example, identical protein binding, kinase binding, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by FAS itself. We selected most functions FAS had, and list some proteins which have the same functions with FAS. You can find most of the proteins on our site.

FAS has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with FAS here. Most of them are supplied by our site. Hope this information will be useful for your research of FAS.

FADD