Reference - Detail
| RRC ID | 38457 |
|---|---|
| Author | Motani K, Kushiyama H, Imamura R, Kinoshita T, Nishiuchi T, Suda T. |
| Title | Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity. |
| Journal | 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. |
| Volume | 286(39) |
| Pages | 33963-72 |
| Published | 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 |
| Times Cited | 39 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Resource | |
| Human and Animal Cells | KU812(RCB0495) |