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) |