Inhibition of the canonical Wnt signaling pathway in cytoplasm: a novel property of the carboxyl terminal domains of two Xenopus ELL genes.
The Wnt signaling pathways are important in many developmental events. The canonical Wnt pathway is one of the three major Wnt-mediated intracellular signaling pathways and is thought to activate Dvl followed by the stabilization of beta-catenin. In Xenopus, this pathway is involved in dorsal determination, anterior-posterior patterning during gastrulation, and neural induction. Here we describe a role for the Xenopus ELL (Eleven-nineteen Lysine-rich Leukemia) gene product in canonical Wnt signaling. Translocation of ELL has been associated with acute myeloid leukemia and the protein possesses three functional domains. We identified rELL-C from a rat brain cDNA library as a binding factor for Dishevelled (Dvl); it represents a partial sequence of rat ELL lacking the pol II elongation domain and has been shown to suppress canonical Wnt signaling. Next, we isolated two Xenopus homologs of ELL, xELL1 and xELL2. No obvious phenotypes were observed with microinjection of full-length xELL1 or xELL2 mRNA, however, microinjection with their occludin homology domain inhibited Wnt signaling at the level of Dvl and upstream of beta-catenin. Intracellular localization of microinjected xELL1- and xELL2-GFP mRNAs showed localization of the full-length products in the nucleus and the occludin-homology domain products in cytoplasm. These results raise the possibility that ELL, which is thought to function as a transcription factor in nuclei, can serve other, novel roles to suppress canonical Wnt signaling in the cytoplasm.
Sakurai
Kenji
K
Department of Biology, Graduate School of Science, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Michiue
Tatsuo
T
Kikuchi
Akira
A
Asashima
Makoto
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000072261:Dishevelled Proteins; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008845:Microinjections; D008969:Molecular Sequence Data; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism* / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D004268:DNA-Binding Proteins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; C488331:ELL protein, Xenopus; C488332:ELL2 protein, Xenopus; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D029867:Xenopus Proteins