The extrinsic pathway for programmed cell death

• The extrinsic signaling pathway leading to apoptosis involves transmembrane death receptors that are members of the tumor necrosis factor (TNF) receptor gene superfamily. Members of this receptor family bind to extrinsic ligands and transduce intracellular signals that ultimately result in the destruction of the cell (Figure 2)^7,8
• The most well characterized ligands of these receptors to date are FasL, TNF-alpha, Apo3L, and Apo2L. Corresponding receptors are FasR, TNFR1, DR3, and DR4/DR5, respectively^5-7
  • Molecules that stimulate the activity of these pro-apoptotic proteins or activate these receptors are currently under evaluation for their therapeutic potential in the treatment of cancer, including hematologic malignancies
• The signal transduction of the extrinsic pathway involves several caspases which are proteases with specific cellular targets. Once activated, the caspases affect several cellular functions as part of a process that results in the death of the cells⁵

Figure 2. Elements of the extrinsic apoptotic pathway.⁹

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