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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Priya, Rangasamy Sneha Desai, Pavitra Anbarasu, Kumaraswamy Rajabather, Suryaraja Mahalingam, Sundarasamy Datta, Debduti |
| Description | Author Affiliation: Datta D ( From the Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600 036, India.); Anbarasu K ( From the Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600 036, India.); Rajabather S ( From the Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600 036, India.); Priya RS ( From the Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600 036, India.); Desai P ( From the Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600 036, India.); Mahalingam S ( From the Laboratory of Molecular Virology and Cell Biology, National Cancer Tissue Biobank, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology-Madras, Chennai 600 036, India mahalingam@iitm.ac.in.) |
| Abstract | 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. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 35 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-08-28 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Nucleolus Metabolism Cyclin-Dependent Kinase Inhibitor P21 G1 Phase GTP-Binding Proteins Nuclear Proteins S Phase Cell Cycle Checkpoints Cell Proliferation Cyclin D1 Cyclin-Dependent Kinase 4 DNA-Binding Proteins Down-Regulation Gene Expression Regulation Gene Knockdown Techniques HEK293 Cells MCF-7 Cells Models, Biological Protein Stability Proteolysis Ribosomal Proteins Tumor Suppressor Protein P53 Up-Regulation Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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