Table 1.
Deregulated factors and pathways in CRC.
| Regulators of mRNA Translation | Deregulation in CRC | Impact on mRNA Translation | |
|---|---|---|---|
| Ribosomal Components | RPL15 | upregulation | enhanced ribosome biogenesis |
| RPL22 | mutation, downregulation | potentially deregulated translation of pro-apoptotic proteins and metastasis-related proteins | |
| RPS20 | mutation | defect in pre-ribosomal RNA maturation | |
| RPS24 | upregulation | enhanced ribosome biogenesis | |
| ribosomal RNAs | upregulation via MYC-mediated deregulation of RNA pol I and III activity | enhanced ribosome biogenesis | |
| Signaling Pathways and Associated Factors | RAS/MAPK signaling | mutation and hyperactivation | hyperactivation of mTORC1 and subsequent activation of p70-S6K1 and inhibition of 4E-BPs leading to enhanced translation initiation |
| PI3K/AKT signaling | mutation and hyperactivation, upregulation | hyperactivation of mTORC1 and subsequent activation of p70-S6K1 and inhibition of 4E-BPs leading to enhanced translation initiation | |
| PTEN | deletion | upregulation of PI3K/AKT signaling | |
| mTORC1 | mutation and hyperactivation, overexpression, increased phosphorylation of mTOR | activation of p70-S6K1 and inhibition of 4E-BPs leading to enhanced translation initiation | |
| 4E-BPs | increased phosphorylation | release of eIF4E and enhanced translation initiation | |
| PDCD4 | downregulation | enhanced eIF4A activity and translation initiation | |
| p70-S6K1 | increased phosphorylation | phosphorylation and inactivation of PDCD4 and eEF2K and enhanced translation initiation and elongation | |
| Translation Elongation Factors | eEF2K | downregulation | enhanced activity of eEF2 and translation elongation |
| eEF2 | upregulation | enhanced translation elongation | |
| Translation Initiation Factors | eIF4E | upregulation, increased phosphorylation at S209 | enhanced translation initiation |
| eIF4A1 | upregulation | enhanced translation initiation | |
| eIF2α | upregulation, increased phosphorylation at S51 | sequestration of eIF2B in an inactive complex, thereby limiting high translation rates | |
| eIF2B complex | upregulation | enhanced complex formation with p-eIF2α | |
| Stress-related Kinase | GCN2 | increased activity | increased phosphorylation of eIF2α |
Summary of important ribosomal components, signaling proteins as well as translation factors, their deregulation and impact on protein synthesis in CRC.