Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function

Abstract

Current understanding of the mechanisms by which cell growth is regulated lags significantly behind our knowledge of the complex processes controlling cell cycle progression. Recent studies suggest that the mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth via the regulation of protein synthesis. The key mTOR effectors of cell growth are eukaryotic initiation factor 4E-binding protein 1 (4EBP-1) and the ribosomal protein S6 kinase (S6K). Here we will review the current models for mTOR dependent regulation of ribosome function and biogenesis as well as its role in coordinating growth factor and nutrient signaling to facilitate homeostasis of cell growth and proliferation. We will place particular emphasis on the role of S6K1 signaling and will highlight the points of cross talk with other key growth control pathways. Finally, we will discuss the impact of S6K signaling and the consequent feedback regulation of the PI3K/Akt pathway on disease processes including cancer.