CD95

Overview

CD95, also known as Fas receptor or APO-1, is a cell surface receptor that plays a crucial role in the regulation of programmed cell death, or apoptosis. It is a member of the tumor necrosis factor receptor superfamily and is encoded by the FAS gene in humans. CD95 is widely expressed in various tissues and is essential for maintaining immune system homeostasis and preventing autoimmune diseases.

Structure

CD95 is a type I transmembrane protein composed of an extracellular domain, a transmembrane domain, and a cytoplasmic domain. The extracellular domain is responsible for binding to its ligand, Fas ligand (FasL), which is a type II transmembrane protein belonging to the tumor necrosis factor (TNF) family. The cytoplasmic domain contains a death domain, which is crucial for transmitting apoptotic signals inside the cell.

Function

The primary function of CD95 is to induce apoptosis in cells that express the receptor. Upon binding to FasL, CD95 undergoes trimerization, which leads to the recruitment of the adaptor protein FADD (Fas-associated death domain). FADD then recruits procaspase-8, forming the death-inducing signaling complex (DISC). Activation of procaspase-8 initiates a cascade of caspase activation, ultimately leading to cell death.

CD95-mediated apoptosis is vital for the elimination of infected or cancerous cells and for the regulation of the immune response. Dysregulation of CD95 signaling can result in various pathological conditions, including autoimmune diseases, cancer, and immune deficiency disorders.

Clinical Significance

Mutations or alterations in the FAS gene can lead to impaired apoptosis and are associated with several diseases. For example, mutations in the FAS gene are linked to Autoimmune Lymphoproliferative Syndrome (ALPS), a disorder characterized by the accumulation of lymphocytes due to defective apoptosis.

In cancer, tumor cells may evade apoptosis by downregulating CD95 expression or by expressing decoy receptors that inhibit FasL binding. Therapeutic strategies targeting the CD95 pathway are being explored to enhance apoptosis in cancer cells.

Research and Therapeutic Applications

Research on CD95 has led to the development of potential therapeutic interventions aimed at modulating apoptosis. These include agonistic antibodies that mimic FasL to induce apoptosis in cancer cells and inhibitors that block CD95 signaling in diseases where excessive apoptosis is detrimental.

Also see

• Apoptosis
• Fas ligand
• Tumor necrosis factor receptor superfamily
• Autoimmune Lymphoproliferative Syndrome
• Caspases