دورية أكاديمية
Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation
| العنوان: | Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation |
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| المؤلفون: | López de la Oliva, Amada R., Campos-Sandoval, José A., Gómez-García, María C., Cardona, Carolina, Martín-Rufián, Mercedes, Sialana, Fernando J., Castilla, Laura, Bae, Narkhyun, Lobo, Carolina, Peñalver, Ana, García-Frutos, Marina, Carro, David, Enrique, Victoria, Paz, José C., Mirmira, Raghavendra G., Gutiérrez, Antonia, Alonso, Francisco J., Segura, Juan A., Matés, José M., Lubec, Gert, Márquez, Javier |
| المساهمون: | López de la Oliva,AR, Gómez-García,MC, Cardona,C, Castilla,L, Peñalver,A, García-Frutos,M, Carro,D, Enrique,V, Paz,JC, Alonso,FJ, Segura,JA, Matés,JM, Márquez,J Departamento de Biología Molecular y Bioquímica, Canceromics Lab, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain and Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. Campos-Sandoval,JA, Martín-Rufián,M, Lobo,C Proteomics Lab, Central Facility Core, University of Málaga, Málaga, Spain. Sialana,FJ, Lubec,G Private Medical University of Salzburg, Salzburg, Austria. Bae,N Institute of Science and Technology Austria, Klosterneuburg, Austria. Mirmira,RG Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA. Gutiérrez,A Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA). Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Málaga, Spain. |
| بيانات النشر: | Springer |
| سنة النشر: | 2020 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | Translocation, Glutaminase, Cell Proliferation, Cell cycle, Mitochondria, Cancer, Translocación genética, Glutaminasa, Proliferación celular, Ciclo celular, Mitocondrias, Animals, COS Cells, Carcinogenesis, Cell Line, Tumor, Hep G2 Cells, Humans, Neoplasms, Cell Cycle Checkpoints, Cell Differentiation |
| الوصف: | Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | https://www.nature.com/articles/s41598-020-58264-4Test; http://hdl.handle.net/10668/3878Test; http://hdl.handle.net/20.500.12105/18000Test; Scientific Reports |
| DOI: | 10.1038/s41598-020-58264-4 |
| الإتاحة: | https://doi.org/20.500.12105/18000Test https://doi.org/10.1038/s41598-020-58264-4Test http://hdl.handle.net/10668/3878Test https://hdl.handle.net/20.500.12105/18000Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ ; Attribution 4.0 International ; open access |
| رقم الانضمام: | edsbas.C093E706 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-020-58264-4 |