When translation meets transformation: the mTOR story.
There is currently a high level of interest in signalling through the mammalian target of rapamycin (mTOR). This reflects both its key role in many cell functions and its involvement in disease states such as cancers. The best understood targets for mTOR signalling are proteins involved in controlling the translational machinery, including the ribosomal protein S6 kinases and proteins that regulate the initiation and elongation phases of translation. Indeed, there is compelling evidence that at least one of these targets of mTOR (eukaryotic initiation factor eIF4E) plays a key role in tumorigenesis. It is regulated through the mTOR-dependent phosphorylation of inhibitory proteins such as eIF4E-binding protein 1. Thus, targeting mTOR signalling may be an effective anticancer strategy, in at least a significant subset of tumours. Not all effects of mTOR are sensitive to the classical anti-mTOR drug rapamycin, and this compound also interferes with other processes besides eIF4E function. Developing new approaches to targeting mTOR for cancer therapy requires more detailed knowledge of signalling downstream of mTOR. Such advances are likely to come from further work to understand the regulation of mTOR targets such as components of the translational apparatus.
Averous
J
J
Unité de Nutrition Humaine, INRA de Theix, Saint Genès Champanelle, France.
Proud
C G
CG
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D006801:Humans; D008954:Models, Biological; D010445:Peptide Elongation Factors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014170:Transformation, Genetic
D010445:Peptide Elongation Factors; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human