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Published online 28 July 2003. doi:10.1083/jcb.200303157
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© The Rockefeller University Press, 0021-9525/2003/8/457 $5.00
The Journal of Cell Biology, Volume 162, Number 3, 457-467


Article

Regulation of the expression and processing of caspase-12

Michael Kalai, Mohamed Lamkanfi, Geertrui Denecker, Michael Boogmans, Saskia Lippens, Ann Meeus, Wim Declercq and Peter Vandenabeele

Department of Molecular Biomedical Research, Unit of Molecular Signalling and Cell Death, VIB and Ghent University, B-9000 Ghent, Belgium

Address correspondence to Peter Vandenabeele, Department of Molecular Biomedical Research, Unit of Molecular Signalling and Cell Death, Ghent University, Ledeganckstraat 35, B-9000 Ghent, Belgium. Tel.: 32-9-264-51-31. Fax: 32-9-264-53-48. email: peter.vandenabeele{at}dmb.rug.ac.be

Phylogenetic analysis clusters caspase-12 with the inflammatory caspases 1 and 11. We analyzed the expression of caspase-12 in mouse embryos, adult organs, and different cell types and tested the effect of interferons (IFNs) and other proinflammatory stimuli. Constitutive expression of the caspase-12 protein was restricted to certain cell types, such as epithelial cells, primary fibroblasts, and L929 fibrosarcoma cells. In fibroblasts and B16/B16 melanoma cells, caspase-12 expression is stimulated by IFN-{gamma} but not by IFN-{alpha} or -ß. The effect is increased further when IFN-{gamma} is combined with TNF, lipopolysaccharide (LPS), or dsRNA. These stimuli also induce caspase-1 and -11 but inhibit the expression of caspase-3 and -9. In contrast to caspase-1 and -11, no caspase-12 protein was detected in macrophages in any of these treatments. Transient overexpression of full-length caspase-12 leads to proteolytic processing of the enzyme and apoptosis. Similar processing occurs in TNF-, LPS-, Fas ligand–, and thapsigargin (Tg)-induced apoptosis. However, B16/B16 melanoma cells die when treated with the ER stress–inducing agent Tg whether they express caspase-12 or not.

Key Words: apoptosis; caspase-12; inflammation; interferon; ER stress


Abbreviations used in this paper: FasL, Fas ligand; IFN, interferon; IL, interleukin; LPS, lipopolysaccharide; Tg, thapsigargin.


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