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Prenylated Rab acceptor 1 (PRA1) inhibits TCF/{beta}-catenin signaling by binding to {beta}-catenin

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [2];  [3];  [3];  [4];  [2];  [1]
  1. Department of Biological Sciences, Sookmyung Women's University, Seoul 140-742 (Korea, Republic of)
  2. Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333 (Korea, Republic of)
  3. Division of Life Science, Pai Chai University, Daejeon 302-735 (Korea, Republic of)
  4. Division of Bioscience and Biotechnology, Konkuk University, Seoul 143-701 (Korea, Republic of)
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.
OSTI ID:
20854514
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 349; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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