Downstream Targets of mTORC1

The best-understood targets for mTOR complex 1 (mTORC1) are proteins that are involved in mRNA translation or in its control. They include the ribosomal protein S6 kinases and the eukaryotic initiation factor (eIF) 4E-binding proteins (4E-BPs). The latter regulate the availability of the cap-binding protein eIF4E and the formation of eIF4F complexes which promote the translation of certain mRNAs. The physiological roles of the S6 kinases are less clear. 4E-BPs and S6 kinases all contain a TOR-signaling (TOS) motif which allows them to interact with the mTORC1 component raptor and facilitates their phosphorylation by mTORC1. Two other proteins, the transcriptional regulator hypoxia-inducible factor (HIF)-1α and proline-rich Akt substrate 40 kDa (PRAS40), also contain TOS motifs and are regulated by mTORC1. Several other processes are also controlled by mTORC1; these include translation elongation (through the regulation of eukaryotic elongation factor (eEF2) kinase), autophagy, and the transcription of genes involved in mitochondrial function. Here, we review current understanding of signaling downstream of mTORC1.