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| Content Provider | PubMed Central |
|---|---|
| Author | Naito, Mikihiko Katayama, Ryohei Ishioka, Toshiyasu Suga, Akiko Takubo, Kohei Nanjo, Masahiro Hashimoto, Chizuko Taira, Masanori Takada, Shinji Takada, Ritsuko Kitagawa, Masatoshi Matsuzawa, Shu-ichi Reed, John C. Tsuruo, Takashi |
| Copyright Year | 2004 |
| Abstract | Cellular FLIP (cFLIP) is a close homologue of caspase 8 without caspase activity that inhibits Fas signaling. The cFLIP protein is often expressed in human tumors and is believed to suppress antitumor immune responses involving the Fas system. Here, we report that a long form of cFLIP (cFLIP-L) inhibits β-catenin ubiquitylation and increases endogenous cytosolic β-catenin, which results in translocation of β-catenin into nuclei and induction of β-catenin-dependent gene expression in cFLIP-L-expressing cells. When cells stably expressing cFLIP-L were stimulated with Wnt3a, enhanced Wnt signaling was observed compared with the control cells. Conversely, depletion of endogenous cFLIP results in reduced Wnt signaling. Furthermore, cFLIP-L increases secondary-body axis formation when coinjected with suboptimal doses of β-catenin into early Xenopus embryos. Down-regulation of FADD by RNA-mediated interference abolishes the β-catenin-dependent gene expression induced by cFLIP-L. These results indicate that cFLIP-L, in cooperation with FADD, enhances canonical Wnt signaling by inhibiting proteasomal degradation of β-catenin, thus suggesting an additional mechanism involved with tumorgenesis, in addition to inhibiting Fas signaling. |
| Related Links | http://dx.doi.org/10.1128/mcb.24.19.8418-8427.2004 |
| Ending Page | 8427 |
| Page Count | 10 |
| Starting Page | 8418 |
| File Format | |
| ISSN | 02707306 |
| e-ISSN | 10985549 |
| Journal | Molecular and Cellular Biology |
| Issue Number | 19 |
| Volume Number | 24 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2004-10-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Cell Biology Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
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