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Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1.
J Biol Chem. 2015 Aug 28; 290(35):21536-52.JB

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+Show Affiliations

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.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.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26203195

Citation

Datta, Debduti, et al. "Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition By Activating Cyclin-dependent Kinase Inhibitor P21 Cip1/Waf1." The Journal of Biological Chemistry, vol. 290, no. 35, 2015, pp. 21536-52.
Datta D, Anbarasu K, Rajabather S, et al. Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1. J Biol Chem. 2015;290(35):21536-52.
Datta, D., Anbarasu, K., Rajabather, S., Priya, R. S., Desai, P., & Mahalingam, S. (2015). Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1. The Journal of Biological Chemistry, 290(35), 21536-52. https://doi.org/10.1074/jbc.M115.637280
Datta D, et al. Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition By Activating Cyclin-dependent Kinase Inhibitor P21 Cip1/Waf1. J Biol Chem. 2015 Aug 28;290(35):21536-52. PubMed PMID: 26203195.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1. AU - Datta,Debduti, AU - Anbarasu,Kumaraswamy, AU - Rajabather,Suryaraja, AU - Priya,Rangasamy Sneha, AU - Desai,Pavitra, AU - Mahalingam,Sundarasamy, Y1 - 2015/07/09/ PY - 2015/01/08/received PY - 2015/7/24/entrez PY - 2015/7/24/pubmed PY - 2015/12/15/medline KW - E2F transcription factor KW - cell cycle KW - mouse double minute 2 homolog (Mdm2) KW - p53 KW - tumor cell biology SP - 21536 EP - 52 JF - The Journal of biological chemistry JO - J Biol Chem VL - 290 IS - 35 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/26203195/Nucleolar_GTP_binding_Protein_1__NGP_1__Promotes_G1_to_S_Phase_Transition_by_Activating_Cyclin_dependent_Kinase_Inhibitor_p21_Cip1/Waf1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)44919-1 DB - PRIME DP - Unbound Medicine ER -