One 4E-BP (4E-BP: KY421373) was found corresponding to vertebrate 4E-BP1
HULC: long non-coding RNA highly upregulated in liver cancer; sh-HULC: pGPU6/GFP/Neo plasmid carrying short-hairpin RNA targeting HULC; sh-NC: pGPU6/GFP/Neo plasmid carrying a non-targeting RNA; pEX-HULC: pEX-2 plasmid carrying full-length HULC; LC3B-II: microtubule-associated protein 1 light chain 3B II; 4E-BP1
: eukaryotic initiation factor 4E binding protein 1; p: phosphorylated.
Most importantly 4E-BP1
and s6k are downstream targets of both AMPK and mTOR, AMPK is an upstream inhibitor of mTOR and Akt's effects on energy metabolism tends to reduce AMP which indirectly inhibit AMPK (Xu et al., 2012).
As observed for MNK1, the inducible phosphorylation of the S6 kinase (and of its substrate, the S6 ribosomal protein) and to a lesser extent the inducible hyperphosphorylation of 4E-BP1
were impaired following STK or Syk inhibition.
Of note, rapalogs only incompletely block mTORC1, as, for example, mTORC1 phosphorylates the Thr-37 and Thr-46 sites of 4E-BP1
that are rapamycin insensitive .
The mTORC1 and mTORC2 activities were assessed by the phosphorylation of their downstream targets, S6RP, p70S6K, 4E-BP1
, and Akt, respectively.
The level of phosphorylated p70S6K and 4E-BP1
, two downstream substrates of mTOR, also significantly decreased after dose- and time-dependently exposure to diosgenin (Fig.
Blenis, "TOS motif-mediated raptor binding regulates 4E-BP1
multisite phosphorylation and function," Current Biology, vol.
mTORC1 consists of four subunits: mTOR, mLST8, PRAS40, and the raptor, each playing an important role in regulating cell growth and proliferation by directly phosphorylating two regulators of protein translation, p70-S6 kinase (p70S6K) and 4E binding protein 1 (4E-BP1
mTORC1 regulates translation by phosphorylating its various downstream effectors, with S6K1 and 4E-BP1
being the most imperative targets.
Quando a 4E-BP1
e fosforilada, o eIF4E e liberado e pode unir-se, ao eIF4G e o qual esta tambem sob o controle do MTOR e ao eIF4A, formando o complexo ribossomal eIF4F.
Yamada et al., "ATF4-mediated induction of 4E-BP1
contributes to pancreatic [beta] cell survival under endoplasmic reticulum stress," Cell Metabolism, vol.