Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1.

Nucleolar GTP-binding protein (NGP-1) is overexpressed in various cancers and proliferating cells, but the functional significance remains unknown. In this study, we show that NGP-1 promotes G1 to S phase transition of cells by enhancing CDK inhibitor p21(Cip-1/Waf1) expression through p53. In addition, our results suggest that activation of the ...
cyclin D1-CDK4 complex by NGP-1 via maintaining the stoichiometry between cyclin D1-CDK4 complex and p21 resulted in hyperphosphorylation of retinoblastoma protein at serine 780 (p-RB(Ser-780)) followed by the up-regulation of E2F1 target genes required to promote G1 to S phase transition. Furthermore, our data suggest that ribosomal protein RPL23A interacts with NGP-1 and abolishes NGP-1-induced p53 activity by enhancing Mdm2-mediated p53 polyubiquitination. Finally, reduction of p-RB(Ser-780) levels and E2F1 target gene expression upon ectopic expression of RPL23a resulted in arrest at the G1 phase of the cell cycle. Collectively, this investigation provides evidence that NGP-1 promotes cell cycle progression through the activation of the p53/p21(Cip-1/Waf1) pathway.
Mesh Terms:
Cell Cycle Checkpoints, Cell Nucleolus, Cell Proliferation, Cyclin D1, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase Inhibitor p21, DNA-Binding Proteins, Down-Regulation, G1 Phase, GTP-Binding Proteins, Gene Expression Regulation, Gene Knockdown Techniques, HEK293 Cells, Humans, MCF-7 Cells, Models, Biological, Nuclear Proteins, Protein Stability, Proteolysis, Ribosomal Proteins, S Phase, Tumor Suppressor Protein p53, Up-Regulation
J. Biol. Chem.
Date: Aug. 28, 2015
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