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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 01, 2009 |
Title |
IL-3 coordination of myeloblast function by modulating mRNA stability |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
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. We used kinetic microarray, Northern Blotting and bioinformatics analysis of IL-3 dependent myeloblasts to determine whether IL-3 acts in part by regulating the rate of turnover of mRNA transcripts in specific functional pathways. Our results indicate that exposure of myeloblasts to IL-3 causes immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Examples include transcripts associated with proliferation and leukemic transformation (pik3cd, myb, pim-1), hematopoietic development (cited2), differentiation control (cdkn1a) and RNA processing (BRF1, BRF2). A domain in the 3’-utr of IL-6 that mediates IL-3 responsiveness contains AU-rich elements that bind proteins known to modulate mRNA stability, however a known destabilizing protein (AUF1) is shown not to mediate degradation in the absence of IL-3. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of this network of transcripts could contribute to growth patterns observed in leukemia.
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Overall design |
Cells were exposed to actinomycin D to block transcription for 0, 2 or 4 hours. The cytokine IL-3 was added after actinomycin D either at a high (1 ng/ml) or low (10 pg/ml) concentration. The effect of cytokine on transcript decay rates was therefore determined. There were five determinations per experiment (0 hour, and 2 hr and 4 hours, the latter two time points at both high and at low IL3); two independent experiments are represented (10 microarray analyses in total).
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Contributor(s) |
Ernst J, Ghanem L, Bar-Joseph Z, McNamara M, Steinman RA |
Citation(s) |
19829692 |
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Submission date |
Jul 10, 2008 |
Last update date |
May 04, 2018 |
Contact name |
Richard A Steinman |
E-mail(s) |
steinman@pitt.edu
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Phone |
412 6233237
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Fax |
412 6237768
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Organization name |
University of Pittsburgh
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Department |
Medicine
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Lab |
2.18 Hillman Cancer Center
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Street address |
5117 Centre Avenue
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City |
Pittsburgh |
State/province |
PA |
ZIP/Postal code |
15213 |
Country |
USA |
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Platforms (1) |
GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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Samples (10)
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GSM304665 |
32D cells time 0 after actinomycin D Experiment 2 |
GSM304666 |
32D cells time 2 hr after actinomycin D, High IL3, Experiment 2 |
GSM304667 |
32D cells time 4 hr after actinomycin D, High IL3, Experiment 2 |
GSM304668 |
32D cells time 2 hr after actinomycin D, Low IL3, Experiment 2 |
GSM304670 |
32D cells time 4 hr after actinomycin D, Low IL3, Experiment 2 |
GSM304672 |
32D cells time 0 after actinomycin D Experiment 1 |
GSM304673 |
32D cells time 2 hr after actinomycin D, High IL3, Experiment 1 |
GSM304674 |
32D cells time 4 hr after actinomycin D, High IL3, Experiment 1 |
GSM304675 |
32D cells time 2 hr after actinomycin D, Low IL3, Experiment 1 |
GSM304676 |
32D cells time 4 hr after actinomycin D, Low IL3, Experiment 1 |
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Relations |
BioProject |
PRJNA113315 |
Supplementary file |
Size |
Download |
File type/resource |
GSE12067_RAW.tar |
17.6 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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