Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Ligation of Fas and Cell Death

Post a Response Save to My Folders

The TNF response, NF-kappa B and Bcl-2

28 June 2000

Tomas Jelinek

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?

Post a Response Save to My Folders

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882