title: Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1.
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.
authors.affiliation: 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.
authors.forename: Debduti
authors.initials: D
authors.lastname: Datta
authors.affiliation: 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.
authors.forename: Kumaraswamy
authors.initials: K
authors.lastname: Anbarasu
authors.affiliation: 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.
authors.forename: Suryaraja
authors.initials: S
authors.lastname: Rajabather
authors.affiliation: 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.
authors.forename: Rangasamy Sneha
authors.initials: RS
authors.lastname: Priya
authors.affiliation: 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.
authors.forename: Pavitra
authors.initials: P
authors.lastname: Desai
authors.affiliation: 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.
authors.forename: Sundarasamy
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D059447:Cell Cycle Checkpoints; D002466:Cell Nucleolus / Q000378:metabolism*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D016193:G1 Phase; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D012269:Ribosomal Proteins / Q000378:metabolism; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C000592018:LYAR protein, human; C104699:NGP-1 antigen, human; D009687:Nuclear Proteins; C486191:RPL23a protein, human; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D019204:GTP-Binding Proteins
keywords: E2F transcription factor; cell cycle; mouse double minute 2 homolog (Mdm2); p53; tumor cell biology