Modulation of Wnt signaling by the nuclear localization of cellular FLIP-L
| Autor: | Mikihiko Naito, Ryohei Katayama, Naoya Fujita, Toshiyasu Ishioka, Ritsuko Takada, Takashi Tsuruo, Shinji Takada |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cytoplasm
Active Transport Cell Nucleus CASP8 and FADD-Like Apoptosis Regulating Protein Receptors Cytoplasmic and Nuclear Apoptosis Karyopherins Protein Sorting Signals Biology environment and public health Cell Line medicine Humans NLS Cloning Molecular Nuclear export signal Cell Nucleus Wnt signaling pathway LRP6 LRP5 Cell Biology Cell biology Wnt Proteins Protein Transport medicine.anatomical_structure Fatty Acids Unsaturated Mutant Proteins Nucleus Nuclear localization sequence Signal Transduction |
| Zdroj: | Journal of Cell Science. 123:23-28 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.058602 |
| Popis: | Cellular FLIP (cFLIP) inhibits the apoptosis signaling initiated by death receptor ligation. We previously reported that a long form of cFLIP (cFLIP-L) enhances Wnt signaling via inhibition of β-catenin ubiquitylation. In this report, we present evidence that cFLIP-L translocates into the nucleus, which could have a role in modulation of Wnt signaling. cFLIP-L has a functional bipartite nuclear localization signal (NLS) at the C-terminus. Wild-type cFLIP-L (wt-FLIP-L) localizes in both the nucleus and cytoplasm, whereas NLS-mutated cFLIP-L localizes predominantly in the cytoplasm. cFLIP-L also has a nuclear export signal (NES) near the NLS, and leptomycin B, an inhibitor of CRM1-dependent nuclear export, increases the nuclear accumulation of cFLIP-L, suggesting that it shuttles between the nucleus and cytoplasm. Expression of mutant cFLIP-L proteins with a deletion or mutations in the NLS and NES confers resistance to Fas-mediated apoptosis, as does wt-FLIP-L, but they do not enhance Wnt signaling, which suggests an important role of the C-terminus of cFLIP-L in Wnt-signaling modulation. When wt-FLIP-L is expressed in the cytoplasm by conjugation with exogenous NES (NES-FLIP-L), Wnt signaling is not enhanced, whereas the NES-FLIP-L increases cytoplasmic β-catenin as efficiently as wt-FLIP-L. cFLIP-L physically interacts with the reporter plasmid for Wnt signaling, but not with the control plasmid. These results suggest a role for nuclear cFLIP-L in the modulation of Wnt signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|