Involvement of CPP32/Yama(-like) proteases in Fas-mediated apoptosis.

Abstract	Fas (Apo-1/CD95) belongs to the tumor necrosis factor/nerve growth factor receptor family and transmits apoptotic signals by binding to its ligand. Interleukin-1beta-converting enzyme (ICE), which shows substantial homology to the product of the cell death gene, ced-3, of Caenorhabditis elegans, is reported to be involved in Fas-mediated apoptosis. Using two human carcinoma-derived cell lines with undetectable levels of ICE, we found that an agonistic antihuman Fas antibody induces the activation of CPP32/Yama(-like) proteases that are ICE(-like) protease family members, and that a tetrapeptide inhibitor of CPP32/Yama protease, DEVD-CHO, inhibits the Fas-mediated activation of the proteases, Fas-mediated apoptosis, and CPP32/Yama(-like) proteolytic activities in vitro. Fas-mediated apoptosis is inhibited by the CPP32/Yama inhibitor DEVD-CHO, but not by the ICE inhibitor YVAD-CHO, suggesting a dominant role for the CPP32/Yama(-like) proteases and not ICE itself in Fas-mediated apoptosis of the human carcinoma cell lines.
Authors	J Hasegawa, S Kamada, W Kamiike, S Shimizu, T Imazu, H Matsuda, Y Tsujimoto
Journal	Cancer research (Cancer Res) Vol. 56 Issue 8 Pg. 1713-8 (Apr 15 1996) ISSN: 0008-5472 [Print] United States
PMID	8620480 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Enzyme Inhibitors Enzyme Precursors Oligopeptides Recombinant Proteins fas Receptor L 709049 CASP3 protein, human Caspase 3 Caspases Cysteine Endopeptidases Caspase 1
Topics	Amino Acid Sequence Animals Apoptosis (physiology) Blotting, Northern Caenorhabditis elegans (genetics) Carcinoma, Hepatocellular Caspase 1 Caspase 3 Caspases Cell Death (genetics) Cysteine Endopeptidases (biosynthesis, metabolism) Enzyme Inhibitors (pharmacology) Enzyme Precursors (biosynthesis, metabolism) Gene Expression HeLa Cells Humans Kinetics Liver Neoplasms Molecular Sequence Data Oligopeptides (pharmacology) Recombinant Proteins (metabolism) Structure-Activity Relationship Transfection Tumor Cells, Cultured fas Receptor (physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!