2020年3月1日 · TPDHT induces apoptosis and cell cycle arrest by targeting ERK/MNK/eIF4F. The eIF4E/eIF4G complex plays a central role in gene expression regulation during the initial stage of translation.

The precise mechanism by which eIF4E induces onco-genic transformation remains unclear, but some evidence suggests that the Akt/mTOR and ERK/Mnk1 pathways regulate the activity of eIF4E [23,25,28]. eIF4E is an important target for oncogenic translational deregulation in PI3K/AKT/mTOR and RAS/MEK signaling pathways, which act on the downstream ...

Our results indicate that TPDHT could disrupt the interaction of eIF4E/eIF4G, and the activity of eIF4F plays an important role in TPDHT-induced cell proliferation inhibition and apoptosis. Further research showed that TPDHT could inhibit the Ras/ERK/MNK pathway, and activation of the ERK pathway reversed TPDHT-induced cell proliferation ...

2025年3月4日 · MNK activity is regulated by the p38 and Erk MAPK pathways. Phosphorylation of MNK leads to its activation and binding to the eIF4G/eIF4E complex. MNK then phosphorylates eIF4E at Ser209, whose activation is associated with oncogene translation, leading to tumorigenesis. Given this important role for eIF4E in tumorigenesis, MNK inhibition with novel small molecule inhibitors could be a ...

Active MAPK signaling can modulate eIF4F activity via the ERK/MNK axis, promoting eIF4E phosphorylation at Ser209 (19–22). Although we assumed that highly active ERK signaling driven by oncogenic mutations might already fully stimulate eIF4E phosphorylation, we tested the possibility that the increase in ERK activity after eIF4Fi action could ...

2018年10月23日 · The mRNA cap-binding protein, eukaryotic translation initiation factor 4E (eIF4E), is involved in the recruitment of the ribosome to the mRNA cap structure, playing a central role in the regulation of translation initiation. eIF4E integrates inputs from the mTOR and ERK signaling pathways, both of which are activated in numerous painful ...

2020年9月1日 · Extracellular signal–regulated kinases (ERKs, including ERK 1 and ERK2) are activated downstream of oncoproteins such as receptor tyrosine kinases, Ras and Raf, and in turn drive MNK1 activation and eIF4E phosphorylation. The p38 MAP kinases α and β are activated by stress signals such as arsenite and anisomycin and various cytokines [15].

Translation initiation, the rate limiting step in protein synthesis, is dependent on the activity of eukaryotic translation Initiation Factor 4E (eIF4E). eIF4E is the cap-binding protein which, in synergy with proteins such as the helicase eIF4A and the scaffolding protein eIF4G, binds to mRNA, allowing the recruitment of ribosomes and translati...

2019年9月23日 · We propose that MNK-eIF4E signalling is a core, evolutionarily conserved, signalling module that controls nociceptor plasticity. This finding has important implications for the therapeutic potential of this target, and it provides interesting clues about the evolutionary origins of mechanisms important for pain-related plasticity.

2024年12月17日 · MNK activity is regulated by the p38 and Erk MAPK pathways. Phosphorylation of MNK leads to its activation and binding to the eIF4G/eIF4E complex. MNK then phosphorylates eIF4E at Ser209, whose activation is associated with oncogene translation, leading to tumorigenesis. Given this important role for eIF4E in tumorigenesis, MNK inhibition with ...