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NF‐κB protects from the lysosomal pathway of cell death
Author(s) -
Liu Ni,
Raja Srikumar M.,
Zazzeroni Francesca,
Metkar Sunil S.,
Shah Ramila,
Zhang Manling,
Wang Yue,
Brömme Dieter,
Russin William A.,
Lee Justine C.,
Peter Marcus E.,
Froelich Christopher J.,
Franzoso Guido,
AshtonRickardt Philip G.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg510
Subject(s) - biology , cathepsin b , lysosome , microbiology and biotechnology , cathepsin , programmed cell death , apoptosis , cathepsin s , cathepsin d , caspase , nf κb , downregulation and upregulation , caspase 8 , signal transduction , cathepsin l , biochemistry , gene , enzyme
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.