Signaling control of mRNA translation in cancer pathogenesis

Therapeutic targets: MTOR and related pathways

“…17 However, recent studies indicate that the translation of TOP mRNAs may occur independent of S6K1 function (see recent reviews ref. 18). S6K1 may play a role in glucose homeostasis and regulation of eukaryotic elongation factor 2 kinase.…”

The Cap-Dependent Translation Apparatus Integrates and Amplifies Cancer Pathways

“…The cytoplasmic interaction of eIF4E and eIF4G is also a target for regulation of cap-dependent translation by extracellular signals and metabolic cues. 7,8,27,28 Both the formation and integrity of eIF4F are determined largely by the abundance of eIF4E and its propensity to associate with eIF4G. Two primary mechanisms regulating the association of eIF4E with eIF4G are recognized: (a) transcriptional control of eIF4E abundance and (b) binding of eIF4G competitors to eIF4E.…”

“…In the past five years, it has become evident that cancer is also subject to translational control. [3][4][5][6][7][8][9][10][11] As a result, attention has focused on the rate-limiting step in the process of protein synthesis, translation initiation. Here, we will discuss cancer-related regulatory events mediated by the mRNA binding stage of translation initiation.…”

Aberrant mRNA translation in cancer pathogenesis: an old concept revisited comes finally of age

“…The various chapters describe how the detailed knowledge of the molecular mechanisms and the signaling pathways which control mRNA translation and the protein synthetic machinery have identified steps potentially involved in tumorigenesis, in turn pointing at novel 'druggable targets' for cancer therapy (Bader and Vogt, 2004;Clemens, 2004;De Benedetti and Graff, 2004;Fingar and Blenis, 2004;Holland et al, 2004;Mamane et al, 2004;Perrotti and Calabretta, 2004;Rajasekhar and Holland, 2004;Rosenwald, 2004;Schmidt, 2004;Stoneley and Willis, 2004;White, 2004). Virtually all the reviews focus on the role that deregulated mRNA translation control may play in oncogenesis, describing the work performed in eukaryotic cells and mammalian systems.…”