RRC ID 38457
著者 Motani K, Kushiyama H, Imamura R, Kinoshita T, Nishiuchi T, Suda T.
タイトル Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity.
ジャーナル J Biol Chem
Abstract 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.
巻・号 286(39)
ページ 33963-72
公開日 2011-9-30
DOI 10.1074/jbc.M111.286823
PII S0021-9258(20)73943-8
PMID 21832064
PMC PMC3190783
MeSH Adaptor Proteins, Signal Transducing Amino Acid Chloromethyl Ketones / pharmacology CARD Signaling Adaptor Proteins Carrier Proteins / genetics Carrier Proteins / metabolism Caspase 1 / genetics Caspase 1 / metabolism* Caspase 8 / genetics Caspase 8 / metabolism Caspase Inhibitors Cell Line, Tumor Cysteine Proteinase Inhibitors / pharmacology Cytoskeletal Proteins / biosynthesis* Cytoskeletal Proteins / genetics Dipeptides / pharmacology Gene Expression Regulation* Gene Knockdown Techniques Humans Interleukin-1beta / genetics Interleukin-1beta / metabolism NLR Family, Pyrin Domain-Containing 3 Protein Necrosis / genetics Necrosis / metabolism Pseudomonas Infections / genetics Pseudomonas Infections / metabolism Repressor Proteins / genetics Repressor Proteins / metabolism Staphylococcal Infections / genetics Staphylococcal Infections / metabolism
IF 4.238
引用数 39
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 KU812(RCB0495)