TRAIL Mouse

TRAIL was first identified through a screen of an expressed sequence tag database using a conserved sequence within several TNF family members . It was subsequently named Apo2L due to its close homology to the Fas/Apolipoprotein (Apo) 1 ligand . Structurally, TRAIL is a type II transmembrane protein that can be cleaved to form a soluble ligand. The biologically active form of TRAIL is multimeric (or cross-linked), rather than monomeric .

TRAIL induces apoptosis by binding to its cognate receptors on the cell surface. These receptors include death receptor 4 (DR4) and death receptor 5 (DR5), which are also known as TRAIL-R1 and TRAIL-R2, respectively . Upon binding to these receptors, TRAIL triggers the formation of a membrane-bound macromolecular complex called the death-inducing signaling complex (DISC). This complex is necessary and sufficient to engage the apoptotic machinery .

Interestingly, TRAIL also interacts with decoy receptors (DcR1 and DcR2), which can antagonize its interaction with DR4 and DR5 . These decoy receptors lack the intracellular death domain required for apoptosis signaling, thereby acting as inhibitors of TRAIL-induced apoptosis.

The pro-apoptotic signaling of TRAIL through DR4 and DR5 is regulated by glycosylation. Both N-linked and O-linked glycosylation sites are present on these receptors, and these post-translational modifications play a crucial role in regulating receptor/receptor interactions and trafficking . This regulation ultimately defines cell fate through TRAIL stimulation.

TRAIL has generated considerable interest as a potential anticancer agent due to its ability to selectively induce apoptosis in cancer cells. This selective induction of cell death makes TRAIL an attractive candidate for cancer therapy, as it can potentially overcome resistance to internal triggers of apoptosis after radiation or chemotherapy . Researchers are actively exploring the therapeutic applications of TRAIL and its receptors, aiming to develop innovative anticancer therapies .