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- Title
NF-?B protects from the lysosomal pathway of cell death.
- Authors
Ni Liu; Raja, Srikumar M.; Zazzeroni, Francesca; Metkar, Sunil S.; Shah, Ramila; Manling Zhang; Yue Wang; Brömme, Dieter; Russin, William A.; Lee, Justine C.; Peter, Marcus E.; Froelich, Christopher J.; Franzoso, Guido; Ashton-Rickardt, Philip G.
- Abstract
The programme of gene expression induced by RelA/ NF-κB transcription factors is critical to the control of cell survival. Ligation of 'death receptors' such as tumor necrosis factor receptor 1 (TNF-R1) triggers apoptosis, as well as NF-κB, which counteracts this process by activating the transcription of anti-apoptotic genes. In addition to activating caspases, TNF-R1 stimulation causes the release of cathepsins, most notably cathepsin B, from the lysosome into the cytoplasm where they induce apoptosis. Here we report a mechanism by which NF-κB protects cells against TNF-a-induced apoptosis: inhibition of the lysosomal pathway of apoptosis. NF-κB can protect cells from death after TNF-R1 stimulation, by extinguishing cathepsin B activity in the cytosol. This activity of NF-κB is mediated, at least in part, by the upregulation of Serine protease inhibitor 2A (Spi2A), a potent inhibitor of cathepsin B. Indeed, Spi2A can substitute for NF-κB in suppressing the induction of cathepsin B activity in the cytosol. Thus, inhibition of cathepsin B by Spi2A is a mechanism by which NF-κB protects cells from lysosome-mediated apoptosis.
- Subjects
LYSOSOMAL storage diseases; CELL death; GENE expression; NF-kappa B; LYSOSOMES; ORGANELLES
- Publication
EMBO Journal, 2003, Vol 22, Issue 19, p5313
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/cdg510