Deletion of p37Ing1 in Mice Reveals a p53-Independent Role for Ing1 in the Suppression of Cell Proliferation, Apoptosis, and Tumorigenesis
| Autor: | Zhiqing Zhu, Concetta G.A. Marfella, Andrew H. Coles, Stephen N. Jones, Huiling Liang, Anthony N. Imbalzano, Joonsoo Kang |
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| Rok vydání: | 2007 |
| Předmět: |
Cell physiology
Cancer Research Programmed cell death Tumor suppressor gene Apoptosis Biology medicine.disease_cause Article Mice medicine Animals Cellular Senescence Cell Line Transformed Cell Proliferation Mice Knockout Cell growth Tumor Suppressor Proteins Intracellular Signaling Peptides and Proteins Nuclear Proteins Proto-Oncogene Proteins c-mdm2 Embryo Mammalian Chromatin Cell biology Mice Inbred C57BL Cell Transformation Neoplastic Oncology Cell culture Cancer research Tumor Suppressor Protein p53 Carcinogenesis Inhibitor of Growth Protein 1 DNA Damage |
| Zdroj: | Cancer Research. 67:2054-2061 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-06-3558 |
| Popis: | ING proteins have been proposed to alter chromatin structure and gene transcription to regulate numerous aspects of cell physiology, including cell growth, senescence, stress response, apoptosis, and transformation. ING1, the founding member of the inhibitor of growth family, encodes p37Ing1, a plant homeodomain (PHD) protein that interacts with the p53 tumor suppressor protein and seems to be a critical cofactor in p53-mediated regulation of cell growth and apoptosis. In this study, we have generated and analyzed p37Ing1-deficient mice and primary cells to further explore the role of Ing1 in the regulation of cell growth and p53 activity. The results show that endogenous levels of p37Ing1 inhibit the proliferation of p53-wild-type and p53-deficient fibroblasts, and that p53 functions are unperturbed in p37Ing1-deficient cells. In addition, loss of p37Ing1 induces Bax expression and increases DNA damage–induced apoptosis in primary cells and mice irrespective of p53 status. Finally, p37Ing1 suppresses the formation of spontaneous follicular B-cell lymphomas in mice. These results indicate that p53 does not require p37Ing1 to negatively regulate cell growth and offers genetic proof that Ing1 suppresses cell growth and tumorigenesis. Furthermore, these data reveal that p37Ing1 can negatively regulate cell growth and apoptosis in a p53-independent manner. [Cancer Res 2007;67(5):2054–61] |
| Databáze: | OpenAIRE |
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