Regulation of TNFR1 and CD95 signalling by receptor compartmentalization

Tumour-necrosis factor receptor-1 (TNFR1) and CD95 can transduce pro-apoptotic and anti-apoptotic signals, but what determines the specificity of signalling events? It is possible that the endosomal compartment functions as a signalling organelle that selectively transmits death signals from TNFR1 and CD95. The death receptors tumour-necrosis factor receptor-1 (TNFR1) and CD95 (also known as FAS and APO-1) transduce signals that promote cell death by apoptosis. However, these receptors are also capable of inducing anti-apoptotic signals through the activation of the transcription factor nuclear factor-κB (NF-κB) or through activation of the proliferative mitogen-activated protein kinase (MAPK) cascade. Recent findings reveal a role for receptor internalization and endosomal trafficking in selectively transmitting the signals that lead either to apoptosis or to the survival of the cell.