@article{oai:kanazawa-u.repo.nii.ac.jp:00027372,
 author = {今村, 龍 and 木下, 健 and 須田, 貴司 and Hasegawa, Mizuho and Kawase, Kouji and Inohara, Naohiro and Imamura, Ryu and Yeh, Wen-Chen and Kinoshita, Takeshi and Suda, Takashi},
 issue = {12},
 journal = {Oncogene Volume},
 month = {Mar},
 note = {Apoptosis-associated speck-like protein containing a CARD (ASC) is an adaptor molecule that mediates apoptotic and inflammatory signals, and implicated in tumor suppression. However, the mechanism of ASC-mediated apoptosis has not been well elucidated. Here, we investigated the molecular mechanisms of ASC-mediated apoptosis in several cell lines using a caspase recruitment domain 12-Nod2 chimeric protein that transduces the signal from muramyl dipeptide into ASC-mediated apoptosis. Experiments using dominant-negative mutants, small-interfering RNAs and peptide inhibitors for caspases indicated that caspase-8 was generally required for ASC-mediated apoptosis, whereas a requirement for caspase-9 depended on the cell type. In addition, caspase-like apoptosis-regulatory protein (CLARP)/Fas-like inhibitor protein, a natural caspase-8 inhibitor, suppressed ASC-mediated apoptosis, and Clarp-/- mouse embryonic fibroblasts were highly sensitive to ASC-mediated apoptosis. Bax-deficient HCT116 cells were resistant to ASC-mediated apoptosis as reported previously, although we failed to observe colocalization of ASC and Bax in cells. Like Fas-ligand-induced apoptosis, the ASC-mediated apoptosis was inhibited by Bcl-2 and/or Bcl-XL in type-II but not type-I cell lines. Bid was cleaved upon ASC activation, and suppression of endogenous Bid expression using small-interfering RNAs in type-II cells reduced the ASC-mediated apoptosis. These results indicate that ASC, like death receptors, mediates two types of apoptosis depending on the cell type, in a manner involving caspase-8. © 2007 Nature Publishing Group All rights reserved., 金沢大学がん研究所がん病態制御},
 pages = {1748--1756},
 title = {Mechanism of ASC-mediated apoptosis: Bid-dependent apoptosis in type II cells},
 volume = {26},
 year = {2007}
}