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dc.contributor.authorErnst, Jason
dc.contributor.authorGhanem, Louis
dc.contributor.authorBar-Joseph, Ziv
dc.contributor.authorMcNamara, Michael
dc.contributor.authorBrown, Jason
dc.contributor.authorSteinman, Richard A.
dc.date.accessioned2010-03-18T16:56:47Z
dc.date.available2010-03-18T16:56:47Z
dc.date.issued2009-10
dc.date.submitted2009-03
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1721.1/52709
dc.description.abstractThe 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) 39-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.en
dc.description.sponsorshipHillman Foundationen
dc.language.isoen_US
dc.publisherPublic Library of Scienceen
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0007469en
dc.rightsCreative Commons Attributionen
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en
dc.sourcePLoSen
dc.titleIL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stabilityen
dc.typeArticleen
dc.identifier.citationErnst J, Ghanem L, Bar-Joseph Z, McNamara M, Brown J, et al. 2009 IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Altering mRNA Stability. PLoS ONE 4(10): e7469. doi:10.1371/journal.pone.0007469en
dc.contributor.departmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratoryen_US
dc.contributor.approverErnst, Jason
dc.contributor.mitauthorErnst, Jason
dc.relation.journalPLoS ONEen
dc.eprint.versionFinal published versionen
dc.identifier.pmid19829692
dc.type.urihttp://purl.org/eprint/type/JournalArticleen
eprint.statushttp://purl.org/eprint/status/PeerRevieweden
dspace.orderedauthorsErnst, Jason; Ghanem, Louis; Bar-Joseph, Ziv; McNamara, Michael; Brown, Jason; Steinman, Richard A.en
dspace.mitauthor.errortrue
mit.licensePUBLISHER_CCen
mit.metadata.statusComplete


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