Staurosporine inhibits phosphorylation of translational regulators linked to mTOR

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Treatment of Swiss 3T3 cells with staurosporine resulted in dephosphorylation of two proteins which play key roles in regulating mRNA translation. This occurred before the execution of apoptosis, assessed by caspase-3 activity. These translation regulators are p70 S6 kinase, which phosphorylates ribosomal protein S6, and eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1), which both lie downstream of the mammalian target of rapamycin (mTOR). This resulted in decreased p70 S6 kinase activity, dephosphorylation of ribosomal protein S6, increased binding of 4E-BP1 to elF4E and a concomitant decrease in elF4F complexes. Our data show that staurosporine impairs mTOR signalling in vivo but that this not due to direct inhibition of mTOR or to inhibition of protein kinase C. It is becoming clear that agents which cause apoptosis inactivate mTOR signalling as a common early response prior to the execution of apoptosis, i.e., before caspase activation.

Original languageEnglish
Pages (from-to)841-849
Number of pages9
JournalCell Death and Differentiation
Volume8
Issue number8
DOIs
Publication statusPublished - 20 Aug 2001

Keywords

  • Apoptosis
  • Initiation factor
  • PKC
  • Staurosporine
  • mRNA translation
  • mTOR

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this