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Mol Cell Biol
2004 Oct 01;2419:8418-27. doi: 10.1128/MCB.24.19.8418-8427.2004.
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Cellular FLIP inhibits beta-catenin ubiquitylation and enhances Wnt signaling.
Naito M
,
Katayama R
,
Ishioka T
,
Suga A
,
Takubo K
,
Nanjo M
,
Hashimoto C
,
Taira M
,
Takada S
,
Takada R
,
Kitagawa M
,
Matsuzawa S
,
Reed JC
,
Tsuruo T
.
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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 beta-catenin ubiquitylation and increases endogenous cytosolic beta-catenin, which results in translocation of beta-catenin into nuclei and induction of beta-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 beta-catenin into early Xenopus embryos. Down-regulation of FADD by RNA-mediated interference abolishes the beta-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 beta-catenin, thus suggesting an additional mechanism involved with tumorgenesis, in addition to inhibiting Fas signaling.
Adachi,
Enhanced and accelerated lymphoproliferation in Fas-null mice.
1996, Pubmed
Adachi,
Enhanced and accelerated lymphoproliferation in Fas-null mice.
1996,
Pubmed
Bullani,
Selective expression of FLIP in malignant melanocytic skin lesions.
2001,
Pubmed
Cadigan,
Wnt signaling: a common theme in animal development.
1997,
Pubmed
,
Xenbase
Clevers,
Axin and hepatocellular carcinomas.
2000,
Pubmed
,
Xenbase
Djerbi,
The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors.
1999,
Pubmed
French,
Inhibition of death receptor signaling by FLICE-inhibitory protein as a mechanism for immune escape of tumors.
1999,
Pubmed
Funayama,
Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling.
1995,
Pubmed
,
Xenbase
Goltsev,
CASH, a novel caspase homologue with death effector domains.
1997,
Pubmed
Groden,
Identification and characterization of the familial adenomatous polyposis coli gene.
1991,
Pubmed
Hamada,
Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin.
1999,
Pubmed
Han,
MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death.
1997,
Pubmed
Hiratani,
Functional domains of the LIM homeodomain protein Xlim-1 involved in negative regulation, transactivation, and axis formation in Xenopus embryos.
2001,
Pubmed
,
Xenbase
Hu,
I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis.
1997,
Pubmed
Hurlstone,
The Wnt/beta-catenin pathway regulates cardiac valve formation.
2003,
Pubmed
Ikeda,
Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin.
1998,
Pubmed
Irmler,
Inhibition of death receptor signals by cellular FLIP.
1997,
Pubmed
Kataoka,
The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways.
2000,
Pubmed
Kataoka,
FLIP prevents apoptosis induced by death receptors but not by perforin/granzyme B, chemotherapeutic drugs, and gamma irradiation.
1998,
Pubmed
Kim,
An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis.
2002,
Pubmed
Kinzler,
Identification of FAP locus genes from chromosome 5q21.
1991,
Pubmed
Kitagawa,
An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.
1999,
Pubmed
Korinek,
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
1997,
Pubmed
Lickert,
Formation of multiple hearts in mice following deletion of beta-catenin in the embryonic endoderm.
2002,
Pubmed
Maedler,
FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication.
2002,
Pubmed
Medema,
Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein.
1999,
Pubmed
Morin,
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.
1997,
Pubmed
Mueller,
Distinct molecular mechanisms of Fas resistance in murine B lymphoma cells.
2000,
Pubmed
Nagata,
Apoptosis by death factor.
1997,
Pubmed
Nishisho,
Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.
1991,
Pubmed
Peifer,
Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus.
2000,
Pubmed
Polakis,
The oncogenic activation of beta-catenin.
1999,
Pubmed
Polakis,
Wnt signaling and cancer.
2000,
Pubmed
Rasper,
Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex.
1998,
Pubmed
Rubinfeld,
Stabilization of beta-catenin by genetic defects in melanoma cell lines.
1997,
Pubmed
Ryu,
Increased expression of cFLIP(L) in colonic adenocarcinoma.
2001,
Pubmed
Satoh,
AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1.
2000,
Pubmed
Scaffidi,
The role of c-FLIP in modulation of CD95-induced apoptosis.
1999,
Pubmed
Shibamoto,
Cytoskeletal reorganization by soluble Wnt-3a protein signalling.
1998,
Pubmed
Shu,
Casper is a FADD- and caspase-related inducer of apoptosis.
1997,
Pubmed
Srinivasula,
FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.
1997,
Pubmed
Tago,
Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
2000,
Pubmed
,
Xenbase
Tepper,
Modulation of caspase-8 and FLICE-inhibitory protein expression as a potential mechanism of Epstein-Barr virus tumorigenesis in Burkitt's lymphoma.
1999,
Pubmed
Thome,
Regulation of lymphocyte proliferation and death by FLIP.
2001,
Pubmed
Varfolomeev,
Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally.
1998,
Pubmed
Wodarz,
Mechanisms of Wnt signaling in development.
1998,
Pubmed
,
Xenbase
Yeh,
Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development.
2000,
Pubmed
Yeh,
FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis.
1998,
Pubmed
Zeng,
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
1997,
Pubmed
,
Xenbase
