NF‐κB protects from the lysosomal pathway of cell death

By Ni Liu, S. Raja, F. Zazzeroni, S. Metkar, Ramila Shah, Manling Zhang, Yue Wang, D. Brömme, W. Russin, Justine C. Lee and 4 more. EMBO Journal, 2003

103 citations recorded by the source corpus.

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‐α‐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.

Subfields: Cancer Research, Molecular Biology, Parasitology

View Paper: https://www.semanticscholar.org/paper/93a2a2b9d99ebbf9b16ec8902b4c557c00d5c12e

How researchers see this paper

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In Cancer Research

1. Guido Kroemer
2. M. Jäättelä

In Molecular Biology

1. Guido Kroemer
2. P. Boya
3. M. Jäättelä
4. L. Galluzzi
5. Douglas R. Green
6. Beth Levine
7. Simone Fulda

In Parasitology

1. Guido Kroemer
2. M. Jäättelä

Citations in the corpus

• Lysosomal cell death at a glance (2013, background): “Examples of genetically confirmed cellular models for lysosomal cell death Stimulus Cell type Protective modification LMP References Activators of death-receptor Anti-Fas HeLa CTSD antisense n.d. (Deiss et al., 1996) TNF WEHI-S Ctsb antisense CSTA cDNA Yes (Foghsgaard et al., 2001) ME180as CTSB anti”
• Lysosomes and autophagy in cell death control (2005, background): “33 ), whereas TNF-induced NF-κB (nuclear factor of κB) activation triggers the expression of the mouse serine protease inhibitor clade A, member 3G (also known as serpina3g), which antagonizes cathepsin B and cathepsin”
• Lysosomal membrane permeabilization in cell death (2008, background): “Similarly, the transfection-enforced overexpression of an endogenous CB inhibitory protein, Spi2a, can reduce LMP in TNF-a-treated cells (Liu et al., 2003).”