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IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability

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Ernst, J and Ghanem, L and Bar-Joseph, Z and McNamara, M and Brown, J and Steinman, RA (2009) IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability. PLoS ONE, 4 (10).

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Abstract

The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3′-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/ Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth. © 2009 Ernst et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ernst, J
Ghanem, L
Bar-Joseph, Z
McNamara, M
Brown, J
Steinman, RAsteinman@pitt.eduSTEINMAN
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBlagosklonny, Mikhail V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 15 October 2009
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 4
Number: 10
DOI or Unique Handle: 10.1371/journal.pone.0007469
Refereed: Yes
MeSH Headings: Amino Acid Motifs; Animals; Computational Biology--methods; Extracellular Signal-Regulated MAP Kinases--metabolism; Gene Expression Regulation, Neoplastic; Granulocyte Precursor Cells--metabolism; Humans; Interleukin-3--metabolism; MAP Kinase Kinase 1--metabolism; Mice; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-abl--metabolism; RNA Processing, Post-Transcriptional; RNA Stability--genetics; Response Elements
Other ID: NLM PMC2758590
PubMed Central ID: PMC2758590
PubMed ID: 19829692
Date Deposited: 03 Aug 2012 16:22
Last Modified: 02 Feb 2019 16:58
URI: http://d-scholarship.pitt.edu/id/eprint/13278

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