|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0017337,
umls-concept:C0021747,
umls-concept:C0033684,
umls-concept:C0040649,
umls-concept:C0083725,
umls-concept:C0085113,
umls-concept:C0376298,
umls-concept:C0679058,
umls-concept:C1515877,
umls-concept:C1547699,
umls-concept:C1879547,
umls-concept:C2700640
|
|
pubmed:issue |
49
|
|
pubmed:dateCreated |
2004-11-25
|
|
pubmed:abstractText |
Deficiency of the interferon consensus sequence-binding protein (ICSBP) is associated with increased myeloid cell proliferation in response to hematopoietic cytokines. However, previously identified ICSBP target genes do not indicate a mechanism for this "cytokine hypersensitivity." In these studies, we identify the gene encoding neurofibromin 1 (Nf1) as an ICSBP target gene, by chromatin immunoprecipitation. Additionally, we find decreased Nf1 expression in bone marrow-derived myeloid cells from ICSBP-/- mice. Since Nf1 deficiency is also associated with cytokine hypersensitivity, our results suggested that NF1 is a functionally significant ICSBP target gene. Consistent with this, we find that the hypersensitivity of ICSBP-/- myeloid cells to granulocyte monocyte colony-stimulating factor (GM-CSF) is reversed by expression of the Nf1 GAP-related domain. We also find that treatment of ICSBP-deficient myeloid cells with monocyte colony-stimulating factor (M-CSF) results in sustained Ras activation, ERK phosphorylation, and proliferation associated with impaired Nf1 expression. These M-CSF effects are reversed by ICSBP expression in ICSBP-/- cells. Consistent with this, we find that ICSBP activates the NF1 promoter in myeloid cell line transfectants and identify an ICSBP-binding NF1 cis element. Therefore, the absence of ICSBP leads to Nf1 deficiency, impairing down-regulation of Ras activation by GM-CSF or M-CSF. These results suggest that one mechanism of increased myeloid proliferation, in ICSBP-deficient cells, is decreased NF1 gene transcription. This novel ICSBP function provides insight into regulation of myelopoiesis under normal conditions and in myeloproliferative disorders.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Neurofibromin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-8,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
3
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
50874-85
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:15371411-Animals,
pubmed-meshheading:15371411-Blotting, Western,
pubmed-meshheading:15371411-Bone Marrow Cells,
pubmed-meshheading:15371411-Cell Nucleus,
pubmed-meshheading:15371411-Cell Proliferation,
pubmed-meshheading:15371411-Cells, Cultured,
pubmed-meshheading:15371411-Chromatin Immunoprecipitation,
pubmed-meshheading:15371411-Cloning, Molecular,
pubmed-meshheading:15371411-Cytokines,
pubmed-meshheading:15371411-DNA, Complementary,
pubmed-meshheading:15371411-Dose-Response Relationship, Drug,
pubmed-meshheading:15371411-Genes, Reporter,
pubmed-meshheading:15371411-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:15371411-Humans,
pubmed-meshheading:15371411-Immunoprecipitation,
pubmed-meshheading:15371411-Interferon Regulatory Factors,
pubmed-meshheading:15371411-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:15371411-Mice,
pubmed-meshheading:15371411-Mice, Knockout,
pubmed-meshheading:15371411-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:15371411-Neurofibromin 1,
pubmed-meshheading:15371411-Oligonucleotides,
pubmed-meshheading:15371411-Phosphorylation,
pubmed-meshheading:15371411-Plasmids,
pubmed-meshheading:15371411-Promoter Regions, Genetic,
pubmed-meshheading:15371411-Protein Structure, Tertiary,
pubmed-meshheading:15371411-RNA,
pubmed-meshheading:15371411-Repressor Proteins,
pubmed-meshheading:15371411-Retroviridae,
pubmed-meshheading:15371411-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15371411-Transcription, Genetic,
pubmed-meshheading:15371411-Transfection,
pubmed-meshheading:15371411-U937 Cells,
pubmed-meshheading:15371411-ras Proteins
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
The interferon consensus sequence-binding protein activates transcription of the gene encoding neurofibromin 1.
|
|
pubmed:affiliation |
Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University and Chicago Lakeside Veterans Affairs Hospital, Chicago, Illinois 60611, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|
