Table 1.
Elements of Cellular Pathways That Regulate Translation-Initiation in the Interferon System
| Initiation regulators | Kinase | Site and sequence | Function | References |
|---|---|---|---|---|
| 4E-BP1 | mTOR, RSK1 | Thr37/T46 | Repressor of mRNA translation and negative regulator of IFN-antiviral responses. Dissociation from eIF4E enables mRNA translation to proceed, leading to induction of expression of certain ISG products | Lekmine and others (2003); Lekmine and others (2004); Thyrell and others (2004); Kaur and others (2007); Burke and others (2011); Kroczynska and others (2011) |
| YSTT*PGGTLFSTT*PGG | ||||
| Thr70 | ||||
| NSPVTKT*PPR | ||||
| Ser65 | ||||
| LMECRNS*PVT | ||||
| eIF4E | MNKs | Ser209 | Requirement for mRNA expression of certain ISGs and generation of IFN-growth inhibitory responses | Joshi and others (2009); Joshi and others (2011); Mehrotra and others (2013) |
| TATKSGS*TTK | ||||
| eIF4B | S6K1, RSK1 | S422 | Increase interaction with eIF3A, ATPase activity, and anti-leukemic effects of IFNs | Kroczynska and others (2011) |
| ERSRTGS*ESS | ||||
| PDCD4 | S6K1, RSK | S67 | Suppressive effects on mRNA translation of certain ISGs. Negative regulation on IFN-antileukemic responses | Kroczynska and others (2012) |
| RRLRKNS*SRD | ||||
| rpS6 | S6K1, S6K2, RSK | S235/S236 | Not well-defined role in mRNA translation | Lekmine and others (2003); Lekmine and others (2004); Kaur and others (2008a); Goncharova and others (2010) |
| AKRRRLS*S*LRA, | ||||
| S240/S244, S247 | ||||
| LSSLRAS*TSKS*ESS*QK |
Indicated phosphorylation sites and sequences are for human proteins.
eIF4B, eukaryotic translation initiation factor 4B; eIF4F, eukaryotic translation initiation factor 4F; IFN, interferon; mTOR, mechanistic target of rapamycin; RSK, ribosomal S6 kinase; MNK, MAPK interacting kinase.