p53-dependent transcriptional responses to interleukin-3 signaling

Anissa M. Jabbour, Lavinia Gordon, Carmel P. Daunt, Benjamin D. Green, Chung H. Kok, Richard D'Andrea, Paul G. Ekert

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

LanguageEnglish
Article numbere31428
JournalPloS one
Volume7
Issue number2
DOIs
Publication statusPublished - 14 Feb 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Jabbour, A. M., Gordon, L., Daunt, C. P., Green, B. D., Kok, C. H., D'Andrea, R., & Ekert, P. G. (2012). p53-dependent transcriptional responses to interleukin-3 signaling. PloS one, 7(2), [e31428]. https://doi.org/10.1371/journal.pone.0031428
Jabbour, Anissa M. ; Gordon, Lavinia ; Daunt, Carmel P. ; Green, Benjamin D. ; Kok, Chung H. ; D'Andrea, Richard ; Ekert, Paul G. / p53-dependent transcriptional responses to interleukin-3 signaling. In: PloS one. 2012 ; Vol. 7, No. 2.
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Jabbour, AM, Gordon, L, Daunt, CP, Green, BD, Kok, CH, D'Andrea, R & Ekert, PG 2012, 'p53-dependent transcriptional responses to interleukin-3 signaling', PloS one, vol. 7, no. 2, e31428. https://doi.org/10.1371/journal.pone.0031428

p53-dependent transcriptional responses to interleukin-3 signaling. / Jabbour, Anissa M.; Gordon, Lavinia; Daunt, Carmel P.; Green, Benjamin D.; Kok, Chung H.; D'Andrea, Richard; Ekert, Paul G.

In: PloS one, Vol. 7, No. 2, e31428, 14.02.2012.

Research output: Contribution to journalArticle

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Jabbour AM, Gordon L, Daunt CP, Green BD, Kok CH, D'Andrea R et al. p53-dependent transcriptional responses to interleukin-3 signaling. PloS one. 2012 Feb 14;7(2). e31428. https://doi.org/10.1371/journal.pone.0031428