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dc.contributor.authorGarrofé Ochoa, Xènia
dc.contributor.authorCosialls, Ana M
dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorGil, Joan
dc.contributor.authorBoix Torras, Jacint
dc.date.accessioned2015-03-20T18:40:10Z
dc.date.available2015-03-20T18:40:10Z
dc.date.issued2011
dc.identifier.issn1360-8185
dc.identifier.urihttp://hdl.handle.net/10459.1/48085
dc.description.abstractChemical inhibitors of cyclin-dependent kinase (CDK), like roscovitine, are promising drugs in thecontext of new cancer therapies. Roscovitine and related compounds, like seliciclib and olomoucine, are effective inducers of apoptosis in many proliferating cells in culture. These compounds are known to activate the intrinsic or mitochondrial pathway of apoptosis. In order to better characterize this intrinsic pathway, a transcriptional analysis was performed using the reverse transcriptase-multiplex ligation-dependent probe amplification procedure (RT-MLPA). In five cell lines, we detected an early and marked reduction of most transcripts, which is consistent with the disruption of transcription that results from the inhibition of CDK7 and CDK9. However, the mRNA of p53-upregulated modulator of apoptosis (PUMA) gene escaped from this transcription inhibition in neuroblastoma cells with a functional p53 protein. The increase of PUMA mRNA was not found in roscovitine-treated cell lines defective in p53, which underwent apoptosis like their p53 proficient counterparts. In addition, in SH-SY5Y cells, sublethal and lethal concentrations of roscovitine produced equivalent increases of PUMA mRNA and protein. In conclusion, the increased expression of PUMA was not associated with apoptosis induction. On the contrary, mRNA and protein depletion of MCL-1 gene correlated the best with cell demise. Moreover, NOXA protein suffered a far minor decrease than MCL-1. Because of the selective neutr alization of NOXA by MCL-1, we hypothesize that the disruption of this balance is a critical event in apoptosis induction by roscovitine and related compounds.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherSpringer Science Business Media
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1007/s10495-011-0603-3
dc.relation.ispartofApoptosis, 2011, vol. 16, num. 7, p. 660-670
dc.rights(c) Springer Science Business Media, 2011
dc.subjectBcl-2
dc.subjectCDK
dc.subjectRoscovitine
dc.subjectOlomoucine
dc.subjectApoptosis
dc.subject.classificationApoptosi
dc.subject.otherApoptosis
dc.titleTrancriptional modulation of apoptotis regulators by Roscovitine and related compounds
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2015-03-20T18:40:10Z
dc.identifier.idgrec016518
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1007/s10495-011-0603-3


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