Regulation of the expression and processing of caspase-12.

Regulation of the expression and processing of caspase-12.
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DOI:
10.1083/jcb.200303157
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发表时间:
2003-08-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Vandenabeele P
Vandenabeele P
中科院分区:
其他
文献类型:
--
作者:
Kalai M;Lamkanfi M;Denecker G;Boogmans M;Lippens S;Meeus A;Declercq W;Vandenabeele P

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系统发育分析将caspase-12与炎症性caspase 1和11聚在一起。我们分析了caspase-12在小鼠胚胎、成体器官和不同细胞类型中的表达,并测试了干扰素(IFN)和其他促炎刺激的作用。Caspase-12蛋白的组成性表达仅限于某些细胞类型,如上皮细胞、原代成纤维细胞和L929纤维肉瘤细胞。在成纤维细胞和B16/B16黑色素瘤细胞中,Caspase-12的表达受干扰素-γ的刺激,但不受干扰素-α或-β的刺激。当干扰素-γ与肿瘤坏死因子、脂多糖或双链核糖核酸联合使用时,这种作用进一步增强。这些刺激也诱导caspase-1和-11,但抑制caspase-3和-9的表达。与caspase-1和caspase-11相反,在所有这些处理中,巨噬细胞中都没有检测到caspase-12蛋白。全长caspase-12的瞬时过表达导致该酶的蛋白水解性加工和细胞凋亡。类似的过程也发生在肿瘤坏死因子、内毒素、Fas配体和thapsigargin(TG)诱导的细胞凋亡中。然而,无论B16/B16黑色素瘤细胞是否表达caspase-12,在ER应激诱导剂TG处理下,它们都会死亡。
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-γ but not by IFN-α or -β. The effect is increased further when IFN-γ 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.
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