IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability
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 whi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2010
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| Online Access: | http://hdl.handle.net/1721.1/52709 |
| _version_ | 1826204636974940160 |
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| author | Ernst, Jason Ghanem, Louis Bar-Joseph, Ziv McNamara, Michael Brown, Jason Steinman, Richard A. |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Ernst, Jason Ghanem, Louis Bar-Joseph, Ziv McNamara, Michael Brown, Jason Steinman, Richard A. |
| author_sort | Ernst, Jason |
| collection | MIT |
| description | 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) 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. |
| first_indexed | 2024-09-23T12:58:35Z |
| format | Article |
| id | mit-1721.1/52709 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:58:35Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/527092022-09-28T11:15:23Z IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability Ernst, Jason Ghanem, Louis Bar-Joseph, Ziv McNamara, Michael Brown, Jason Steinman, Richard A. Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Ernst, Jason Ernst, Jason 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) 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. Hillman Foundation 2010-03-18T16:56:47Z 2010-03-18T16:56:47Z 2009-10 2009-03 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/52709 Ernst 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.0007469 19829692 en_US http://dx.doi.org/10.1371/journal.pone.0007469 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Ernst, Jason Ghanem, Louis Bar-Joseph, Ziv McNamara, Michael Brown, Jason Steinman, Richard A. IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability |
| title | IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability |
| title_full | IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability |
| title_fullStr | IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability |
| title_full_unstemmed | IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability |
| title_short | IL-3 and Oncogenic Abl Regulate the Myeloblast Transcriptome by Alt= Stability |
| title_sort | il 3 and oncogenic abl regulate the myeloblast transcriptome by alt stability |
| url | http://hdl.handle.net/1721.1/52709 |
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