p53-Dependent transcriptional responses to interleukin-3 signaling.

PloS One
Anissa M JabbourPaul 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 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 ki...Continue Reading

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Citations

Dec 12, 2012·The Journal of Experimental Medicine·Yong YuPentao Liu
Apr 8, 2015·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Ozlen BektasNilgun Sayinalp
Jun 22, 2013·Cell Death and Differentiation·B D GreenP G Ekert
Apr 25, 2018·Cell Death & Disease·Florian SchubertUlrich Maurer

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Datasets Mentioned

BETA
GSE18770

Methods Mentioned

BETA
FCS
flow cytometry

Software Mentioned

Gene Set Enrichment Analysis ( GSEA )
Signaling Pathway Impact Analysis ( SPIA )
R
BeadStudio
Bioconductor
GSEA
arrayQualityMetrics
SPIA

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