Discovery and Optimization of a TRAIL R2 Agonist for Cancer Therapy
TRAIL is a cytokine that induces apoptosis in a wide variety of tumor cells but rarely in normal cells. The TRAIL R2 ligand triggers tumor cell apoptosis independently of the p53 tumor-suppressor gene [1, 2, 3, 4, 5]; thus, peptide agonists may offer a complementary approach to conventional cancer therapy. Ligands belonging to the TNF family are anticipated to function as a homotrimer as suggested by the crystal structures of a subset of the family (TNFα, TNFβ, CD40L, and TRAIL). The TNFR family members are transmembrane proteins. The extracellular domain of the receptors is characterized by the concatenated cysteine-rich domains (CRDs)  that are responsible for ligand binding. TRAIL R2 is a single transmembrane receptor arranged as a homo-trimeric complex on the cell membrane, and TRAIL ligand is a Zn-coordinated trimer . Formation of a complex between TRAIL and its signaling receptors, DR4 and DR5, triggers apoptosis by inducing the oligomerization of...
KeywordsIntracellular Death Domain Carcinoma Cell Line HCT116 Synthetic Dimer Colon Carcinoma Cell Line HCT116 NH4OAc Buffer