Cisplatin inhibits in vitro translation by preventing the formation of complete initiation complex.
Mol Pharmacol
; 43(3): 491-7, 1993 Mar.
Article
em En
| MEDLINE
| ID: mdl-8450839
ABSTRACT
We previously reported that mRNA loses the ability to direct in vitro peptide synthesis after incubation with cisplatin. The present study was designed to determine the step in translation that is affected. The rates of translation reactions inhibited by cisplatin were biphasic, having an initial rate comparable to that of the uninhibited reaction before decreasing. Analysis of cisplatin-inhibited reactions in sucrose density gradients showed a decrease in polyribosome formation. These results are consistent with an inhibition of the initiation step of protein synthesis. Individual steps in initiation were tested by analyzing the formation of ribosomal subunits in sucrose gradients that resolve the incomplete complexes. Cisplatin caused an accumulation of 48 S particles accompanied by a decreased amount of completed 80 S initiation complexes. Similar results were obtained in experiments utilizing radiolabeled methionine or mRNA. We conclude that cisplatin blocks the initiation of translation by preventing the joining of the 60 S ribosomal subunit to the 48 S preinitiation subunit.
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Base de dados:
MEDLINE
Assunto principal:
Iniciação Traducional da Cadeia Peptídica
/
Ribossomos
/
Biossíntese de Proteínas
/
Cisplatino
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article