Universitat de Lleida
    • English
    • català
    • español
  • English 
    • English
    • català
    • español
  • Login
Repositori Obert UdL
View Item 
  •   Home
  • Recerca
  • Medicina Experimental
  • Articles publicats (Medicina Experimental)
  • View Item
  •   Home
  • Recerca
  • Medicina Experimental
  • Articles publicats (Medicina Experimental)
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Trancriptional modulation of apoptotis regulators by Roscovitine and related compounds

Thumbnail
View/Open
016518.pdf (11.47Mb)
Issue date
2011
Author
Garrofé Ochoa, Xènia
Cosialls, Ana M
Ribas i Fortuny, Judit
Gil, Joan
Boix Torras, Jacint
Suggested citation
Garrofé Ochoa, Xènia; Cosialls, Ana M; Ribas i Fortuny, Judit; Gil, Joan; Boix Torras, Jacint; . (2011) . Trancriptional modulation of apoptotis regulators by Roscovitine and related compounds. Apoptosis, 2011, vol. 16, num. 7, p. 660-670. https://doi.org/10.1007/s10495-011-0603-3.
Impact


Web of Science logo    citations in Web of Science

Scopus logo    citations in Scopus

Google Scholar logo  Google Scholar
Share
Export to Mendeley
Metadata
Show full item record
Abstract
Chemical 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.
URI
http://hdl.handle.net/10459.1/48085
DOI
https://doi.org/10.1007/s10495-011-0603-3
Is part of
Apoptosis, 2011, vol. 16, num. 7, p. 660-670
European research projects
Collections
  • Articles publicats (Medicina Experimental) [349]
  • Articles publicats (IRBLleida) [1161]
  • Articles publicats (Grup de Recerca en Neurobiologia Cel·lular) [19]

Contact Us | Send Feedback | Legal Notice
© 2023 BiD. Universitat de Lleida
Metadata subjected to 
 

 

Browse

All of the repositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

Statistics

View Usage Statistics

D'interès

Política institucional d'accés obertDiposita les teves publicacionsDiposita dades de recercaSuport a la recerca

Contact Us | Send Feedback | Legal Notice
© 2023 BiD. Universitat de Lleida
Metadata subjected to