p53-Dependent Transcriptional Responses to Interleukin-3 Signaling
Details
Publication Year 2012-02-14, Volume 7, Issue #2, Page e31428
Journal Title
PLOS ONE
Publication Type
Journal Article
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 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.
Publisher
PUBLIC LIBRARY SCIENCE
Keywords
COLORECTAL-CANCER CELLS; APOPTOTIC RESPONSE; UP-REGULATION; DNA-DAMAGE; PUMA; P53; GENOME; GENES; DEATH; SURVIVAL
WEHI Research Division(s)
Cell Signalling And Cell Death
Rights Notice
Copyright 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.


Creation Date: 2012-02-14 12:00:00
Last Modified: 0001-01-01 12:00:00
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