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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-7-3
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pubmed:abstractText |
Increased fetal hemoglobin expression in adulthood is associated with acute stress erythropoiesis. However, the mechanisms underlying gamma-globin induction during the rapid expansion of adult erythroid progenitor cells have not been fully elucidated. Here, we examined COUP-TFII as a potential repressor of gamma-globin gene after stem cell factor (SCF) stimulation in cultured human adult erythroid progenitor cells. We found that COUP-TFII expression is suppressed by SCF through phosphorylation of serine/threonine phosphatase (PP2A) and correlated well with fetal hemoglobin induction. Furthermore, down-regulation of COUP-TFII expression with small interfering RNA (siRNA) significantly increases the gamma-globin expression during the erythroid maturation. Moreover, SCF-increased expression of NF-YA associated with redox regulator Ref-1 and cellular reducing condition enhances the effect of SCF on gamma-globin expression. Activation of Erk1/2 plays a critical role in SCF modulation of downstream transcriptional factor COUP-TFII, which is involved in the regulation of gamma-globin gene induction. Our data show that SCF stimulates Erk1/2 MAPK signaling pathway, which regulates the downstream repressor COUP-TFII by inhibiting serine/threonine phosphatase 2A activity, and that decreased COUP-TFII expression resulted in gamma-globin reactivation in adult erythropoiesis. These observations provide insight into the molecular pathways that regulate gamma-globin augmentation during stress erythropoiesis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/APEX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Binding Factor,
http://linkedlifedata.com/resource/pubmed/chemical/COUP Transcription Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-(Apurinic or Apyrimidinic...,
http://linkedlifedata.com/resource/pubmed/chemical/NFYA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NR2F2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Stem Cell Factor,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Globins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
2
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pubmed:volume |
114
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
187-94
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pubmed:dateRevised |
2010-9-9
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pubmed:meshHeading |
pubmed-meshheading:19401563-Adult,
pubmed-meshheading:19401563-Base Sequence,
pubmed-meshheading:19401563-Binding Sites,
pubmed-meshheading:19401563-CCAAT-Binding Factor,
pubmed-meshheading:19401563-COUP Transcription Factor II,
pubmed-meshheading:19401563-Cells, Cultured,
pubmed-meshheading:19401563-DNA Primers,
pubmed-meshheading:19401563-DNA-(Apurinic or Apyrimidinic Site) Lyase,
pubmed-meshheading:19401563-Erythroid Precursor Cells,
pubmed-meshheading:19401563-Erythropoiesis,
pubmed-meshheading:19401563-Humans,
pubmed-meshheading:19401563-MAP Kinase Signaling System,
pubmed-meshheading:19401563-Promoter Regions, Genetic,
pubmed-meshheading:19401563-Protein Phosphatase 2,
pubmed-meshheading:19401563-RNA, Messenger,
pubmed-meshheading:19401563-Recombinant Proteins,
pubmed-meshheading:19401563-Stem Cell Factor,
pubmed-meshheading:19401563-Stress, Physiological,
pubmed-meshheading:19401563-Transcriptional Activation,
pubmed-meshheading:19401563-gamma-Globins
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pubmed:year |
2009
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pubmed:articleTitle |
SCF induces gamma-globin gene expression by regulating downstream transcription factor COUP-TFII.
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pubmed:affiliation |
Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-2560, USA.
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pubmed:publicationType |
Journal Article
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