Regulation of the expression and processing of caspase-12.
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 -beta. 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.
Kalai
Michael
M
Department of Molecular Biomedical Research, Unit of Molecular Signalling and Cell Death, Ghent University, Ledeganckstraat 35, B-9000 Ghent, Belgium.
Lamkanfi
Mohamed
M
Denecker
Geertrui
G
Boogmans
Michael
M
Lippens
Saskia
S
Meeus
Ann
A
Declercq
Wim
W
Vandenabeele
Peter
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053454:Caspase 12; D020169:Caspases / Q000096:biosynthesis* / Q000187:drug effects; D002478:Cells, Cultured; D005057:Eukaryotic Cells / Q000187:drug effects / Q000201:enzymology*; D053222:Fas Ligand Protein; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics*; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology*; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008545:Melanoma / Q000201:enzymology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D013312:Stress, Physiological / Q000139:chemically induced / Q000201:enzymology; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019284:Thapsigargin; D007371:Interferon-gamma; C506440:Casp12 protein, mouse; D053454:Caspase 12; D020169:Caspases