Regulation of protein synthesis and the role of eIF3 in cancer
Braz. j. med. biol. res
;
43(10): 920-930, Oct. 2010. ilus
Artigo
em Inglês
| LILACS
| ID: lil-561225
ABSTRACT
Maintenance of cell homeostasis and regulation of cell proliferation depend importantly on regulating the process of protein synthesis. Many disease states arise when disregulation of protein synthesis occurs. This review focuses on mechanisms of translational control and how disregulation results in cell malignancy. Most translational controls occur during the initiation phase of protein synthesis, with the initiation factors being the major target of regulation through their phosphorylation. In particular, the recruitment of mRNAs through the m7G-cap structure and the binding of the initiator methionyl-tRNAi are frequent targets. However, translation, especially of specific mRNAs, may also be regulated by sequestration into processing bodies or stress granules, by trans-acting proteins or by microRNAs. When the process of protein synthesis is hyper-activated, weak mRNAs are translated relatively more efficiently, leading to an imbalance of cellular proteins that promotes cell proliferation and malignant transformation. This occurs, for example, when the cap-binding protein, eIF4E, is overexpressed, or when the methionyl-tRNAi-binding factor, eIF2, is too active. In addition, enhanced activity of eIF3 contributes to oncogenesis. The importance of the translation initiation factors as regulators of protein synthesis and cell proliferation makes them potential therapeutic targets for the treatment of cancer.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Biossíntese de Proteínas
/
Regulação Neoplásica da Expressão Gênica
/
Transformação Celular Neoplásica
Limite:
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2010
Tipo de documento:
Artigo
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