| http://purl.uniprot.org/citations/10498620 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10498620 | http://www.w3.org/2000/01/rdf-schema#comment | "Oncogenic RAS alleles encode proteins that accumulate in the guanosine triphosphate (GTP)-bound state. Because post-translational processing of Ras by farnesyltransferase is essential for biologic function, inhibitors of this enzyme have been developed as rational cancer therapeutics. We have investigated farnesyltransferase inhibitor (FTI) L-744,832 in an in vivo murine model of myeloid leukemia that is associated with inactivation of the Nf1 tumor suppressor gene. Nf1 encodes a GTPase activating protein for Ras, and Nf1-deficient (Nf1-/-) hematopoietic cells show hyperactive Ras signaling through the mitogen-activated protein (MAP) kinase pathway. L-744,832 inhibited H-Ras prenylation in cell lines and in primary hematopoietic cells and abrogated the in vitro growth of myeloid progenitor colonies in response to granulocyte-macrophage colony-stimulating factor (GM-CSF). This FTI also partially blocked GM-CSF-induced MAP kinase activation, but did not reduce constitutively elevated levels of MAP kinase activity in primary Nf1-/-cells. Injection of a single dose of 40 or 80 mg/kg of L-744, 832 increased the amount of unprocessed H-Ras in bone marrow cells, but had no detectable effect on N-Ras. Adoptive transfer of Nf1-/-hematopoietic cells into irradiated mice induces a myeloproliferative disorder that did not respond to L-744,832 treatment. We speculate that the lack of efficacy in this model is due to the resistance of N-Ras and K-Ras processing to inhibition by this FTI."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/author | "Jacks T."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/author | "Kohl N.E."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/author | "Gibbs J.B."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/author | "Taylor B.R."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/author | "Shannon K.M."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/author | "Gratiot M."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/author | "Mahgoub N."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/pages | "2469-2476"xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/title | "In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells."xsd:string |
| http://purl.uniprot.org/citations/10498620 | http://purl.uniprot.org/core/volume | "94"xsd:string |
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