FAS - Fas cell surface death receptor | Elisa - Clia - Antibody - Protein

Background

Fas, also known as CD95 or APO-1, is a cell surface receptor that plays a crucial role in the regulation of programmed cell death (apoptosis). It is a member of the tumor necrosis factor receptor (TNFR) superfamily and is encoded by the FAS gene located on chromosome 10q24.1. The Fas receptor is widely expressed in various tissues and is essential for maintaining immune system homeostasis and eliminating cells that are no longer needed or are potentially harmful. It is particularly important in the regulation of immune responses, where it helps to prevent autoimmune reactions by inducing the death of autoreactive T and B cells.

Protein Structure

• Molecular Weight: Approximately 48 kDa.
• Domains: Fas consists of several domains:
• Extracellular Domain: Contains cysteine-rich domains (CRDs) essential for ligand binding.
• Transmembrane Domain: Anchors the receptor in the cell membrane.
• Intracellular Death Domain (DD): Initiates the apoptotic signaling cascade upon ligand binding.
• Ligand Binding: The extracellular domain binds to Fas ligand (FasL), a type II transmembrane protein that belongs to the TNF family.

Classification and Subtypes

Fas is classified within the TNFR superfamily, which includes receptors that mediate apoptosis and other cellular responses. Fas does not have subtypes, but its ligand, FasL, can exist in both membrane-bound and soluble forms, with the membrane-bound form being more effective at inducing apoptosis.

Function and Biological Significance

• Apoptosis Induction: Fas plays a critical role in apoptosis by binding to FasL. This interaction recruits adaptor proteins like FADD (Fas-associated death domain), which then activates caspase-8, leading to the activation of downstream effector caspases and ultimately cell death.
• Immune Regulation: Fas-mediated apoptosis is essential for the regulation of immune responses. It helps to eliminate autoreactive lymphocytes and maintain tolerance, thereby preventing autoimmune diseases.
• Tissue Homeostasis: By inducing apoptosis, Fas contributes to the removal of damaged or infected cells, playing a vital role in tissue homeostasis and the response to cellular stress.

Clinical Issues

• Autoimmune Diseases: Mutations or deficiencies in Fas or FasL can lead to autoimmune lymphoproliferative syndrome (ALPS), characterized by the accumulation of autoreactive lymphocytes and the development of autoimmune conditions.
• Cancer: Dysregulation of Fas signaling is implicated in cancer. Some tumors evade the immune system by downregulating Fas expression or expressing soluble FasL to inhibit Fas-mediated apoptosis in immune cells.
• Infectious Diseases: Pathogens can exploit the Fas pathway to evade immune responses. For example, some viruses encode proteins that mimic FasL, inducing apoptosis in immune cells and allowing the pathogen to persist.

Summary

Fas is a pivotal receptor in the regulation of apoptosis, essential for immune system function and cellular homeostasis. By binding to its ligand, FasL, it triggers a cascade leading to cell death, thereby eliminating harmful or unnecessary cells. Dysregulation of Fas signaling is associated with various diseases, including autoimmune disorders, cancer, and infectious diseases. Understanding the Fas pathway offers insights into therapeutic targets for managing these conditions.