| p53-Dependent transcriptional responses to interleukin-3 signaling. | |
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MedLine Citation:
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PMID: 22348085 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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p53 is critical in the normal response to a variety of cellular stresses including DNA damage and loss of p53 function is a common feature of many cancers. In hematological malignancies, p53 deletion is less common than in solid malignancies but is associated with poor prognosis and resistance to chemotherapy. Compared to their wild-type (WT) counterparts, hematopoietic progenitor cells lacking p53 have a greater propensity to survive cytokine loss, in part, due to the failure to transcribe Puma, a proapoptotic Bcl-2 family member. Using expression arrays, we have further characterized the differences that distinguish p53(-/-) cells from WT myeloid cells in the presence of Interleukin-3 (IL-3) to determine if such differences contribute to the increased clonogenicity and survival responses observed in p53(-/-) cells. We show that p53(-/-) cells have a deregulated intracellular signaling environment and display a more rapid and sustained response to IL-3. This was accompanied by an increase in active ERK1/2 and a dependence on an intact MAP kinase signaling pathway. Contrastingly, we find that p53(-/-) cells are independent on AKT for their survival. Thus, loss of p53 in myeloid cells results in an altered transcriptional and kinase signaling environment that favors enhanced cytokine signaling. |
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Authors:
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Anissa M Jabbour; Lavinia Gordon; Carmel P Daunt; Benjamin D Green; Chung H Kok; Richard D'Andrea; Paul G Ekert |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-02-14 |
Journal Detail:
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Title: PloS one Volume: 7 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2012 |
Date Detail:
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Created Date: 2012-02-20 Completed Date: 2012-07-31 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e31428 Citation Subset: IM |
Affiliation:
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Children's Cancer Centre, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. jabbour@wehi.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Survival Interleukin-3 / metabolism* MAP Kinase Signaling System Mice Myeloid Cells / cytology, metabolism Proto-Oncogene Proteins c-akt Signal Transduction* Transcription, Genetic* Tumor Suppressor Protein p53 / deficiency, genetics* |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-3; 0/Tumor Suppressor Protein p53; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
| Comments/Corrections | |
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