RRC ID 39607
著者 Li Y, Kanki H, Hachiya T, Ohyama T, Irie S, Tang G, Mukai J, Sato T.
タイトル Negative regulation of Fas-mediated apoptosis by FAP-1 in human cancer cells.
ジャーナル Int J Cancer
Abstract FAP-1 (Fas-associated phosphatase-1) was previously identified as a protein that associates with a negative regulatory domain (C-terminal 15 amino acids) of Fas using the yeast 2-hybrid system. Functional analysis indicated that FAP-1 expression correlates with resistance to Fas-induced apoptosis in human cancer cells. We first generated anti-FAP-1 polyclonal antibody and confirmed the interaction of FAP-1 and Fas in vivo. FAP-1 interacted with wild-type, but not mutant, Fas (tPLV) in 293T cells after transfecting FAP-1 and Fas or its mutant. To investigate the functional role of FAP-1 in Fas-mediated signal transduction, we established stable transfectants of FAP-1 in 3 human cancer cell lines. Apoptosis assays demonstrated that cancer cells over-expressing FAP-1 increased the resistance to Fas-induced apoptosis by the anti-Fas antibody CH-11 in contrast with the wild types or the vector-transfected cells. In addition, FAP-1 regulated the activity of both caspases 3 and 8. Our data indicate a functional role for FAP-1 as a negative regulator of Fas-mediated apoptosis in human cancer cells and suggest that an additional signal-transducing molecule may be required for complete suppression of Fas-mediated apoptosis.
巻・号 87(4)
ページ 473-9
公開日 2000-8-15
DOI 10.1002/1097-0215(20000815)87:4<473::aid-ijc3>3.0.co;2-1
PII 10.1002/1097-0215(20000815)87:4<473::AID-IJC3>3.0.CO;2-1
PMID 10918185
MeSH Antibodies / pharmacology Apoptosis / physiology* Carrier Proteins / genetics Carrier Proteins / immunology Carrier Proteins / physiology* Caspase 3 Caspase 8 Caspase 9 Caspase Inhibitors Caspases / metabolism Humans Jurkat Cells / metabolism Jurkat Cells / pathology Neoplasm Proteins / genetics Neoplasm Proteins / immunology Neoplasm Proteins / physiology Precipitin Tests Protein Phosphatase 1 Protein Tyrosine Phosphatase, Non-Receptor Type 13 Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / immunology Protein Tyrosine Phosphatases / physiology* Signal Transduction / physiology Transfection Tumor Cells, Cultured fas Receptor / immunology fas Receptor / physiology*
IF 5.145
引用数 42
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Hep G2(RCB0459)