Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/73126
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Type: | Journal article |
Title: | p53-dependent transcriptional responses to interleukin-3 signaling |
Author: | Jabbour, A. Gordon, L. Daunt, C. Green, B. Kok, C. D'Andrea, R. Ekert, P. |
Citation: | PLoS One, 2012; 7(2):1-11 |
Publisher: | Public Library of Science |
Issue Date: | 2012 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Hofmann, T.G. |
Statement of Responsibility: | Anissa M. Jabbour, Lavinia Gordon, Carmel P. Daunt, Benjamin D. Green, Chung H. Kok, Richard D’Andrea and Paul G. Ekert |
Abstract: | 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 p532/2 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 p532/2 cells. We show that p532/2 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 p532/2 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. |
Keywords: | Myeloid Cells Animals Mice Interleukin-3 Signal Transduction Cell Survival MAP Kinase Signaling System Transcription, Genetic Tumor Suppressor Protein p53 Proto-Oncogene Proteins c-akt |
Rights: | Copyright: © 2012 Jabbour et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0031428 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0031428 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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hdl_73126.pdf | Published version | 919.38 kB | Adobe PDF | View/Open |
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