NDRG2 and PRA1 interact and synergistically inhibit T-cell factor/β-catenin signaling.
NDRG2 is a member of the N-myc downstream regulated gene (NDRG) family, implicated in cell growth and differentiation. Investigation of NDRG2 molecular interactions by yeast two-hybrid screening identified prenylated Rab acceptor-1 (PRA1), involved in vesicle trafficking and protein transport, as binding partner. Binding of NDRG2 (and NDRG1-4) with PRA1 in vitro was confirmed by GST pull-down assay and immunoprecipitation, and colocalization was verified by confocal microscopy in HCT116 cells. Intracellular coexpression showed that NDRG2 and PRA1 synergistically downregulate T-cell factor (TCF) promoter activity and GSK3β phosphorylation. Results suggest that NDRG2 and PRA1 might act synergistically to prevent signaling of TCF/β-catenin.
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Jong-Tae
JT
Kim
Jae Wha
JW
Kim
Yun Hee
YH
Kang
Kwang Dong
KD
Kim
Seon-Jin
SJ
Lee
Seung-Chul
SC
Choi
Kwang Soo
KS
Kim
Suhn-Kee
SK
Chae
Jung Woo
JW
Kim
Jong-Seok
JS
Lim
Hee Gu
HG
Lee
D021581:Active Transport, Cell Nucleus; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D018613:Microscopy, Confocal; D009154:Mutation; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
C466228:NDRG2 protein, human; D051820:TCF Transcription Factors; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D019204:GTP-Binding Proteins; C108941:RABAC1 protein, human