Ligation of Fas and Cell Death
The TNF response, NF-kappa B and Bcl-2
28 June 2000
Homologous to the Fas pathway is the tumor necrosis factor (TNF)-alpha pathway, using many of the same intracellular effectors that are used by Fas. Yet the work of Baltimore, and Baldwin, suggests that what determines whether TNF- stimulated cells undergo apoptosis or proliferation depends on NF-kappa B, a transcription factor. Any effects of NF-kappa B are of necessity delayed by an hour or so, until transcription and translation of target genes can occur. Among those targets are anti-apoptotic Bcl-family members.
Figuring out how this works mechanistically and kinetically should shed light on the question of Bcl-2 inhibition of the Caspase-8 signal. Specific questions:
1. What is the time-course of activation of the various caspases following Fas (or TNF) administration?
2. When NF-kappa B is involved, what is the time-to-appearance of elevated anti-apoptotic proteins on the mitochondria? Is this time shorter than what is seen for Caspase 9 activation in the absence of NF-kappa B?
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882