Prenylated Rab acceptor 1 (PRA1) inhibits TCF/beta-catenin signaling by binding to beta-catenin.
The prenylated Rab acceptor 1 (PRA1) is a ubiquitously expressed 21 kDa protein containing two transmembrane domains that possibly induce its localization to the Golgi complex. It binds to prenylated Rab GTPases and VAMP2. In this study, we report that PRA1-overexpressing cells exhibited a significantly retarded growth rate as compared to that of the mock-transfected cells, and the transcriptional activity of TCF, as evaluated by TOPflash luciferase reporter assay, was profoundly reduced in the PRA1-overexpressed cells. These intracellular functions of PRA1 were verified by introducing deletion mutant or site-directed mutants, or small interfering RNA of PRA1. In addition, the translocation of beta-catenin from the cytosol to the nucleus was blocked to a significant degree in the PRA1-cells, and the interaction of PRA1 and beta-catenin was identified by confocal microscopy and immunoprecipitation analysis. Finally, we observed that the inhibition of TCF/beta-catenin signaling by PRA1 is associated with ERK1/2 dephosphorylation. Therefore, our data suggest that the in vivo modulation of PRA1 may be involved in TCF/beta-catenin signaling, as well as cellular proliferation and tumorigenesis.
Kim
Jong-Tae
JT
Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Cho
Mi-Young
MY
Choi
Seung-Chul
SC
Kim
Jung Woo
JW
Chae
Suhn-Kee
SK
Yoon
Do-Young
DY
Kim
Jae Wha
JW
Lim
Jong-Seok
JS
D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D051176:beta Catenin; D019204:GTP-Binding Proteins; C108941:RABAC1 protein, human