Regulation of ENT1 expression and ENT1-dependent nucleoside transport by c-Jun N-terminal kinase

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dc.contributor.authorLeisewitz, Andrea V.
dc.contributor.authorZimmerman, Eric I.
dc.contributor.authorHuang, Min
dc.contributor.authorJones, Shannon Z.
dc.contributor.authorYang, Jing
dc.contributor.authorGraves, Lee M.
dc.date.accessioned2024-01-10T13:17:10Z
dc.date.available2024-01-10T13:17:10Z
dc.date.issued2011
dc.description.abstractEquilibrative nucleoside transporters (ENTs) are facilitative transporters broadly selective for pyrimidine and purine nucleosides and are essential for the modulation of nucleoside concentration and nucleoside analog availability. Resistance to nucleoside-derived drugs strongly correlates with a deficiency of ENT1 expression in several tumor cells. Thus, it is crucial to understand the mechanisms by which this transporter is modulated. Using a mouse myeloid leukemic cell line as a model, we investigated whether stress-activated kinases regulate ENT1 expression and function. JNK activation, but not p38 MAPK results in rapid loss of mENT1 function, mRNA expression and promoter activity. c-Jun but not the mutant c-Jun Ser63/73Ala, decreased mENT1 promoter activity. Moreover cJun bound to an AP-1 site identified at -1196 of the promoter, suggesting a specific role for this transcription factor in mENT1 regulation. We propose that activation of JNK-cJun pathway negatively regulates mENT1 and suggest that this mechanism might contribute to the development of nucleoside analog-derived drug resistance. (C) 2010 Elsevier Inc. All rights reserved.
dc.description.funderNIH
dc.description.funderNATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
dc.fechaingreso.objetodigital20-03-2024
dc.format.extent6 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bbrc.2010.11.125
dc.identifier.issn0006-291X
dc.identifier.pubmedidMEDLINE:21145879
dc.identifier.urihttps://doi.org/10.1016/j.bbrc.2010.11.125
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78643
dc.identifier.wosidWOS:000286487700066
dc.information.autorucMedicina;Leisewitz A ;S/I;94860
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final375
dc.pagina.inicio370
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCE
dc.revistaBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
dc.rightsacceso restringido
dc.subjectEquilibrative nucleoside transporter
dc.subjectJNK
dc.subjectChemical stress
dc.subjectChemotherapeutic drugs
dc.subjectSIGNALING PATHWAY
dc.subjectNITRIC-OXIDE
dc.subjectNH2-TERMINAL KINASE
dc.subjectPANCREATIC-CANCER
dc.subjectCELLS
dc.subjectAPOPTOSIS
dc.subjectGENE
dc.subjectGEMCITABINE
dc.subjectPROTEIN
dc.subjectSENSITIVITY
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRegulation of ENT1 expression and ENT1-dependent nucleoside transport by c-Jun N-terminal kinase
dc.typeartículo
dc.volumen404
sipa.codpersvinculados94860
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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