Identifiers
HUGO:EIF4E
eukaryotic translation initiation factor 4E
HUGO:EIF4E, HGNC:3287, ENTREZ:1977, GENECARDS:GC04M099799, UNIPROT:P06730
HUGO:EIF4E HGNC:3287 ENTREZ:1977 UNIPROT:P06730

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
 EMT Senescence   / EMT_REGULATORS 
 EMT Senescence   / MITOCHONDRIA_OXIDATIVE_STRESS 
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
HMC:AVOIDING_IMMUNE_DESTRUCTION
 Innate Immunity   / IMMUNOSTIMULATORY_CORE_PATHWAYS 

References
PMID:9878069
Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E.
PMID:9155017
In vitro, Mnk1 rapidly phosphorylates eIF-4E at the physiologically relevant site, Ser209
Phosphorylation of eIF-4E is believed to enhance its affinity for the 5'-cap
 NATURAL_KILLER 
PMID:15563472
Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells.
Phosphorylation by MNK1 serves to activate eIF4E.eIF4E induces translation of ETS1by recruiting mRNAs to the ribosome,
and upregulates ETS1 protein level.

References
mo_re179:( motility  ) PMID:26597054

References
em_emtc_emtc_re398( EMT Senescence  ):
PMID:9878069
Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E.
PMID:9155017
In vitro, Mnk1 rapidly phosphorylates eIF-4E at the physiologically relevant site, Ser209
em_emtc_emtc_re399( EMT Senescence  ):
PMID:13130303
Regulation of HIF-1a protein synthesis
MNK phosphorylates eIF-4E and stimulates its activity directly.
Active eIF-4E increases the rate of HIF1A-mRNA translation into HIF1A protein.
PMID:16887934
PMID:9159130
HIF-1B (ARNT) is constitutively expressed and itsmRNA and protein are maintained at constant levels regardless of oxygen availability
PMID:9278421
HIF-1A protein has a short half-life (t1/2 = 5 min) and is highly regulated by oxygen
PMID:9746763
The transcription and synthesis of HIF-1B are constitutive and seem not to be affected by oxygen.
PMID:7539918
In normoxia, the HIF-1A proteins are rapidly degraded, resulting in essentially no detectable HIF-1A protein.
PMID:8943284
During hypoxia, HIF-1A becomes stabilized and translocates from the cytoplasm to the nucleus, where it dimerizes with HIF-1B and the HIF complex formed becomes transcriptionally active
PMID:1823643
The activated HIF complex then associates with HREs in the regulatory regions of target genes and binds the transcriptional coactivators to induce gene expression.
PMID:15451019
Tight regulation of the stability and subsequent transactivational function of HIF-1A is chiefly controlled by its post-translation modifications, such as hydroxylation, ubiquitination, acetylation, and phosphorylation
The modification of HIF-1A occurs within several domains.
PMID:10403805
PMID:11566883
PMID:12829734
In normoxia, hydroxylation of 2 proline residues and acetylation of a lysine residue in its ODDD promote interaction of HIF-1A with the von Hippel-Lindau (pVHL) ubiquitin E3 ligase complex (Srinivas et al., 1999; Masson et al., 2001).
PMID:12080085
pVHL complex tags HIF-1A with ubiquitin and thereby marks it for degradation by the 26S proteasome.
In addition, hydroxylation of an asparagine residue in the C-TAD inhibits the association of HIF-1A with CBP/p300 and thus inhibits its transcriptional activity (Lando et al., 2002a).

1. EIF4E@Cytosol
2. EIF4E|​pho@Cytosol

1. EIF4E@INNATE_IMMUNE_CELL_Cytosol
2. EIF4E|​pho|​active@INNATE_IMMUNE_CELL_Cytosol

1. 4E-BP*:​EIF4E@Cytosol

1. 4E-BP1:​EIF4E@Nucleus

1. EIF4E@Cytosol → EIF4E|​pho@Cytosol
2. EIF4E@INNATE_IMMUNE_CELL_Cytosol → EIF4E|​pho|​active@INNATE_IMMUNE_CELL_Cytosol
3. 4E-BP1@Cytosol + EIF4E@Cytosol → 4E-BP1:​EIF4E@Nucleus
4. EIF4E@Cytosol → Capped RNA Translation@Cytosol
5. EIF4E@Cytosol + 4E-BP*@Cytosol → 4E-BP*:​EIF4E@Cytosol
6. EIF4E@Cytosol + EIF4B|​S422_pho@Cytosol → Capped RNA translation@Cytosol

1. rHIF1A@Nucleus → HIF_alpha_*@Cytosol
2. rETS1@INNATE_IMMUNE_CELL_Cytosol → ETS1@INNATE_IMMUNE_CELL_Cytosol