Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors
available in PMC 2012 July 15
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Association of Immunologists
2012
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| Online Access: | http://hdl.handle.net/1721.1/73658 |
| _version_ | 1826190392446418944 |
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| author | Stadanlick, Jason E. Zhang, Zhiqiang Lee, Sang-Yun Hemann, Michael Biery, Matthew Carleton, Michael O. Zambetti, Gerard P. Anderson, Stephen J. Oravecz, Tamas Wiest, David L. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Stadanlick, Jason E. Zhang, Zhiqiang Lee, Sang-Yun Hemann, Michael Biery, Matthew Carleton, Michael O. Zambetti, Gerard P. Anderson, Stephen J. Oravecz, Tamas Wiest, David L. |
| author_sort | Stadanlick, Jason E. |
| collection | MIT |
| description | available in PMC 2012 July 15 |
| first_indexed | 2024-09-23T08:39:35Z |
| format | Article |
| id | mit-1721.1/73658 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:39:35Z |
| publishDate | 2012 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | mit-1721.1/736582022-09-30T10:18:03Z Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors Stadanlick, Jason E. Zhang, Zhiqiang Lee, Sang-Yun Hemann, Michael Biery, Matthew Carleton, Michael O. Zambetti, Gerard P. Anderson, Stephen J. Oravecz, Tamas Wiest, David L. Massachusetts Institute of Technology. Department of Biology Hemann, Michael available in PMC 2012 July 15 alpha beta and gamma delta lineage T cells are thought to arise from a common CD4–CD8– progenitor in the thymus. However, the molecular pathways controlling fate selection and maturation of these two lineages remain poorly understood. We demonstrated recently that a ubiquitously expressed ribosomal protein, Rpl22, is selectively required for the development of alpha beta lineage T cells. Germline ablation of Rpl22 impairs development of alpha beta lineage, but not gamma delta lineage, T cells through activation of a p53-dependent checkpoint. In this study, we investigate the downstream effectors used by p53 to impair T cell development. We found that many p53 targets were induced in Rpl22−/− thymocytes, including miR-34a, PUMA, p21waf, Bax, and Noxa. Notably, the proapoptotic factor Bim, while not a direct p53 target, was also strongly induced in Rpl22−/− T cells. Gain-of-function analysis indicated that overexpression of miR-34a caused a developmental arrest reminiscent of that induced by p53 in Rpl22-deficient T cells; however, only a few p53 targets alleviated developmental arrest when individually ablated by gene targeting or knockdown. Co-elimination of PUMA and Bim resulted in a nearly complete restoration of development of Rpl22−/− thymocytes, indicating that p53-mediated arrest is enforced principally through effects on cell survival. Surprisingly, co-elimination of the primary p53 regulators of cell cycle arrest (p21waf) and apoptosis (PUMA) actually abrogated the partial rescue caused by loss of PUMA alone, suggesting that the G1 checkpoint protein p21[superscript waf] facilitates thymocyte development in some contexts. National Institutes of Health (U.S.) ( (NIH) Grant R01AI073920) National Institutes of Health (U.S.) (NIH Core Grant P01CA06927) National Institutes of Health (U.S.) ( (NIH) Grant R21CA141194) National Institutes of Health (U.S.) ( NIH Center Grant P30-DK-50306) Pennsylvania (appropriation) Fox Chase Cancer Center (NIH Postdoctoral Training Grant T32 CA00903534) Fox Chase Cancer Center (NIH Postdoctoral Training Grant F32 AI089077-01A1) 2012-10-05T18:16:50Z 2012-10-05T18:16:50Z 2011-06 Article http://purl.org/eprint/type/JournalArticle 0022-1767 1550-6606 http://hdl.handle.net/1721.1/73658 Stadanlick, J. E. et al. “Developmental Arrest of T Cells in Rpl22-Deficient Mice Is Dependent Upon Multiple P53 Effectors.” The Journal of Immunology 187.2 (2011): 664–675. Web. en_US http://dx.doi.org/10.4049/jimmunol.1100029 Journal of Immunology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Association of Immunologists PMC |
| spellingShingle | Stadanlick, Jason E. Zhang, Zhiqiang Lee, Sang-Yun Hemann, Michael Biery, Matthew Carleton, Michael O. Zambetti, Gerard P. Anderson, Stephen J. Oravecz, Tamas Wiest, David L. Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors |
| title | Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors |
| title_full | Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors |
| title_fullStr | Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors |
| title_full_unstemmed | Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors |
| title_short | Developmental arrest of T cells in RpL22-deficient mice is dependent upon multiple p53 effectors |
| title_sort | developmental arrest of t cells in rpl22 deficient mice is dependent upon multiple p53 effectors |
| url | http://hdl.handle.net/1721.1/73658 |
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