| http://purl.uniprot.org/citations/18401414 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18401414 | http://www.w3.org/2000/01/rdf-schema#comment | "We examined the involvement of sphingosine kinase-1 (SphK1), which governs the ceramide/sphingosine-1-phosphate balance, in susceptibility to imatinib of either sensitive or resistant chronic myeloid leukemia cells. Imatinib-sensitive LAMA84-s displayed marked SphK1 inhibition coupled with increased content of ceramide and decreased pro-survival sphingosine-1-phosphate. Conversely, no changes in the sphingolipid metabolism were observed in LAMA84-r treated with imatinib. Overcoming imatinib resistance in LAMA84-r with farnesyltransferase or MEK/ERK inhibitors as well as with cytosine arabinoside led to SphK1 inhibition. Overexpression of SphK1 in LAMA84-s cells impaired apoptosis and inhibited the effects of imatinib on caspase-3 activation, cytochrome c and Smac release from mitochondria through modulation of Bim, Bcl-xL and Mcl-1 expression. Pharmacological inhibition of SphK1 with F-12509a or its silencing by siRNA induced apoptosis of both imatinib-sensitive and -resistant cells, suggesting that SphK1 inhibition was critical for apoptosis signaling. We also show that imatinib-sensitive and -resistant primary cells from chronic myeloid leukemia patients can be successfully killed in vitro by the F-12509a inhibitor. These results uncover the involvement of SphK1 in regulating imatinib-induced apoptosis and establish that SphK1 is a downstream effector of the Bcr-Abl/Ras/ERK pathway inhibited by imatinib but upstream regulator of Bcl-2 family members."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.org/dc/terms/identifier | "doi:10.1038/leu.2008.95"xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Martin C."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Kohama T."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Melo J.V."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Cuvillier O."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Malavaud B."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Barnes D.J."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Bonhoure E."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/author | "Lauret A."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/name | "Leukemia"xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/pages | "971-979"xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/title | "Sphingosine kinase-1 is a downstream regulator of imatinib-induced apoptosis in chronic myeloid leukemia cells."xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://purl.uniprot.org/core/volume | "22"xsd:string |
| http://purl.uniprot.org/citations/18401414 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18401414 |
| http://purl.uniprot.org/citations/18401414 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18401414 |
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