| http://purl.uniprot.org/citations/15371411 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15371411 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m405736200"xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/author | "Lu Y."xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/author | "Zhu C."xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/author | "Eklund E.A."xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/author | "Platanias L.C."xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/author | "Saberwal G."xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/pages | "50874-50885"xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/title | "The interferon consensus sequence-binding protein activates transcription of the gene encoding neurofibromin 1."xsd:string |
| http://purl.uniprot.org/citations/15371411 | http://purl.uniprot.org/core/volume | "279"xsd:string |
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