Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins.
AUTOR(ES)
Terada, N
RESUMO
The immunosuppressant rapamycin (RAP) has been demonstrated to specifically inhibit the activity of p70 S6 kinase (p70s6k) and subsequent phosphorylation of ribosomal S6 protein in mammalian cells. Addition of RAP to proliferating lymphoid cells resulted in inhibition of protein synthesis before any changes in the rate of cell proliferation. When the cellular composition of proteins was examined by gel electrophoresis, RAP dramatically inhibited synthesis of selective proteins, particularly elongation factor 2 (eEF-2). The inhibition of eEF-2 synthesis by RAP was at the translational level. Further, RAP inhibited the polysomal association of mRNAs encoding not only eEF-2 but also elongation factor 1-alpha and ribosomal proteins without affecting mRNA translation of any of a number of nonribosomal proteins. Since levels of activity of p70s6k are correlated with the rate of biosynthesis of eEF-2, p70s6k might be involved in coordinate translational regulation of ribosomal protein mRNAs in higher eukaryotes, which have a conserved sequence at their 5' end. Specific inhibition of ribosomal protein synthesis likely explains the differential antiproliferative effect of RAP on proliferating and mitogen-activated quiescent cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=45254Documentos Relacionados
- Glucocorticoids selectively inhibit translation of ribosomal protein mRNAs in P1798 lymphosarcoma cells.
- 5' untranslated leader sequences of eukaryotic mRNAs encoding heat shock induced proteins.
- cDNA clone analysis of six co-regulated mRNAs encoding skeletal muscle contractile proteins.
- Alternatively spliced murine lyn mRNAs encode distinct proteins.
- Translation and the stability of mRNAs encoding the transferrin receptor and c-fos.