BP75, bromodomain-containing M(r) 75,000 protein, binds dishevelled-1 and enhances Wnt signaling by inactivating glycogen synthase kinase-3 beta.
To identify novel regulators of Wnt signaling, we performed yeast two-hybrid analyses with Dvl-1 and identified BP75 as a candidate. Here, we demonstrated that BP75 directly interacts with Dvl-1 in mammalian cells and enhances TCF-dependent gene expression induced by Dvl-1. In support of these results, BP75 in cooperation with Dvl-1 was found to facilitate dephosphorylation at Tyr216 of glycogen synthase kinase-3beta and consequently inhibit its kinase activity. Furthermore, the nuclear translocation and formation of vesicular structures of beta-catenin were induced by BP75 and Dvl-1 in a synergistic manner. Collectively, these results provided us a novel mechanism in Wnt signaling where BP75 plays important regulatory roles between glycogen synthase kinase-3beta and Dvl.
Kim
Sunhong
S
National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yusong, Taejon 305-701, Republic of Korea.
Lee
Jiwoon
J
Park
Jeehye
J
Chung
Jongkyeong
J
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D000072261:Dishevelled Proteins; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism; D000073940:Transcription Factor 4; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000092468:Bromodomain Containing Proteins
D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D000073940:Transcription Factor 4; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C495270:CTNNB1 protein, human; C000606578:DVL1 protein, human; C000606579:Dvl1 protein, mouse; C544894:TCF7L2 protein, human; C090743:Tcf4 protein, mouse; C544895:Tcf7l2 protein, mouse; C000605506:GSK3B protein, human; C000605507:Gsk3b protein, mouse