Caspase-1 Protein Induces Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain (ASC)-mediated Necrosis Independently of Its Catalytic Activity
In: Journal of Biological Chemistry, Jg. 286 (2011-09-01), S. 33963-33972
Online
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Zugriff:
The adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), connects pathogen/danger sensors such as NLRP3 and NLRC4 with caspases and is involved in inflammation and cell death. We have found that ASC activation induced caspase-8-dependent apoptosis or CA-074Me (cathepsin B inhibitor)-inhibitable necrosis depending on the cell type. Unlike necroptosis, another necrotic cell death, ASC-mediated necrosis, was neither RIP3-dependent nor necrostatin-1-inhibitable. Although acetyl-YVAD- chloromethylketone (Ac-YVAD-CMK) (caspase-1 inhibitor) did not inhibit ASC-mediated necrosis, comprehensive gene expression analyses indicated that caspase-1 expression coincided with the necrosis type. Furthermore, caspase-1 knockdown converted necrosis-type cells to apoptosis-type cells, whereas exogenous expression of either wild-type or catalytically inactive caspase-1 did the opposite. Knockdown of caspase-1, but not Ac-YVAD-CMK, suppressed the monocyte necrosis induced by Staphylococcus and Pseudomonas infection. Thus, the catalytic activity of caspase-1 is dispensable for necrosis induction. Intriguingly, a short period of caspase-1 knockdown inhibited IL-1β production but not necrosis, although longer knockdown suppressed both responses. Possible explanations of this phenomenon are discussed. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
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Caspase-1 Protein Induces Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain (ASC)-mediated Necrosis Independently of Its Catalytic Activity
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Autor/in / Beteiligte Person: | Kinoshita, Takeshi ; Suda, Takashi ; Motani, Kou ; Nishiuchi, Takumi ; Imamura, Ryu ; Kushiyama, Hiroko |
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Zeitschrift: | Journal of Biological Chemistry, Jg. 286 (2011-09-01), S. 33963-33972 |
Veröffentlichung: | Elsevier BV, 2011 |
Medientyp: | unknown |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.m111.286823 |
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