IndraLab
Statements
reach
"p70 S6K phosphorylates the ribosomal protein S6 (RPS6), resulting in increased translation of mRNAs containing a 5 ' oligopyrimidine tract, whereas phosphorylation of 4E-BP1 by mTOR relieves inhibition on the initiation factor eIF4E, resulting in more efficient cap dependent translation."
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"Since mTOR phosphorylates 4EBP1, resulting in its dissociation from eIF4E and leading to the formation of the translation initiation complex XREF_BIBR, we used mutant 4EBP1-5A, which lacks the five Ser/Thr phosphorylation sites targeted by mTOR and thus acts as a dominant negative inhibitor by binding elF4E to prevent translation initiation XREF_BIBR."
sparser
"Increased signalling flux through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway leads to an mTOR-dependent phosphorylation of 4E-BP1, which in turn augments its dissociation from eIF4E and stimulates eIF4F complex formation. xref The PI3K/Akt pathway also regulates the availability of eIF4A for eIF4F complex assembly. xref "
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"MTORC1 phosphorylates 4E-BP1 at several residues which promotes the dissociation of eIF4E from 4E-BP1 consequently mitigating the inhibitory effect of 4E-BP1 on eIF4E dependent translation initiation whereas the inhibition of mTOR by rapamycin is believed to cause 4E-BP1 dephosphorylation, which results in inhibition of protein translation (XREF_FIG) [XREF_BIBR]."
sparser
"And recently research showed that c-Myc enhances protein synthesis during tumorigenesis not only through transcriptional control but also by activating mTOR (the mammalian target of rapamycin) -dependent phosphorylation of 4EBP1 (eukaryotic translation initiation factor 4E binding protein 1)."
sparser
"The phosphorylation of S6K1 by mTOR is confined to a single residue (T389)( xref ), and this phosphorylation was eliminated by pemetrexed ( xref ), whereas four residues on 4EBP1 are phosphorylated by mTOR ( xref ); the broader migration pattern seen in pemetrexed-treated cells with the pan-4EBP1 antibody ( xref ) suggests that several of these phosphorylation sites are affected by drug."
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"We found that AKT and mTOR signaling was significantly inhibited in the MMQ and GH3 cells by CAB in a time dependent manner as indicated by decreased phosphorylation of AKT and mTOR as well as decreased phosphorylation of p70S6K and 4EBP1, two key downstream effectors of the mTOR pathway."
sparser
"In addition, mTOR, another substrate subjected to phosphorylation by AKT, enhances phosphorylation of S6K1 and 4E-BP1 [ xref ] and plays crucial roles in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both transcriptional and translational levels [ xref , xref ]."
sparser
"Vam6p (Vps39 in yeast) also functions as a Rag family GTPase nucleotide exchange factor to promote TORC1 activation in response to increased amino acid concentrations in the environment of yeast, leading to mTOR-dependent phosphorylation of the cap-binding protein 4EBP-1 ( xref )."
sparser
"Since S9 is capable of inhibiting the activity of PI3K, we detected whether S9 inhibits the activity of mTOR, which bears a highly homologous COOH-terminal catalytic domain with PI3K. As shown in xref , phosphorylation of 4E-BP1 by mTOR was greatly down-regulated by S9 treatment."
rlimsp
"Consistent with prior studies that have demonstrated that EPO increases mTOR signaling in inflammatory cells [27], [33] and in osteoblastic phenotypes in human bone marrow stromal cells [34], we illustrate that EPO in neuronal cells requires mTOR to phosphorylate p70S6K and 4EBP1."
sparser
"Alleviation of MYC-induced ER stress is driven by enhanced phosphorylated levels of p70S6K and EIF4EBP1 (4E-BP1), a downstream substrate of mammalian target of rapamycin complex 1 (mTORC1) which hyperphosphorylate 4E-BP1 by its dissociation from eIF4E. Targeting the ISR can be achieved by drugging the translational machinery ( xref ) or by targeting autophagy ( xref , xref ), but recently more specific inhibitors of ISR have entered clinical trials."
sparser
"To the extent that the pathway enables LPS-activated macrophages to carry out essential protein translation, it likely works in concert with complementary LPS-induced mechanisms that enhance translation initiation, such as mTOR-induced phosphorylation of 4E-BP1, which activates the initiation factor eIF4E xref ."
rlimsp
"Here, we show that RAFT1 directly phosphorylates p70(S6k), 4E-BP1, and 4E-BP2 and that serum stimulates RAFT1 kinase activity with kinetics similar to those of p70(S6k) and 4E-BP1 phosphorylation. RAFT1 phosphorylates p70(S6k) on Thr-389, a residue whose phosphorylation is rapamycin-sensitive in vivo and necessary for S6 kinase activity. RAFT1 phosphorylation of 4E-BP1 on Thr-36 and Thr-45 blocks its association with the cap-binding protein, eIF-4E, in vitro, and phosphorylation of Thr-45 seems to be the major regulator of the 4E-BP1-eIF-4E interaction in vivo. RAFT1 phosphorylates p70(S6k) much more effectively than 4E-BP1, and the phosphorylation sites on the two proteins show little homology."
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"In addition, mTOR, another substrate subjected to phosphorylation by AKT, enhances phosphorylation of S6K1 and 4E-BP1 [XREF_BIBR] and plays crucial roles in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both transcriptional and translational levels [XREF_BIBR, XREF_BIBR]."
reach
"4E-BP1 and S6K1 are phosphorylated by mammalian target of rapamycin complex 1 (mTORC1) which regulates the binding of eIF4E to the mRNA 5 ' cap through phosphorylation of 4E-BP1 and stimulates protein synthesis through the phosphorylation of S6K1 XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR."
sparser
"When mTOR protein phosphorylates 4E-BP1, it dissociates from eIF4E. Once eIF4E is freed from 4e-BP1, it can form complex structures with several other proteins, including eIF4G or eIF4F. When mTOR phosphorylates p70S6K, this kinase phosphorylates S6 ribosomal protein in return [ xref , xref ]."
sparser
"p70 S6K phosphorylates the ribosomal protein S6 (rpS6), resulting in increased translation of mRNAs containing a 5’ olygopyrimidine tract, whereas phosphorylation of 4E-BP1 by mTOR relieves inhibition on the initiation factor eIF4E resulting in more efficient cap-dependent translation xref ."
sparser
"On the other hand, 4EBP1 binds to the eukaryotic translation initiation factor 4E (EIF4E) to prevent the formation of the translation initiation complex, mTOR phosphorylates 4EBP1 to separate it from EIF4E, thereby forming the translation initiation complex. xref Therefore, we can further deduce that the changes in biological behaviors after RRM2 downregulation may be connected to Akt/mTORC1/4EBP1 signaling pathway."
sparser
"Unlike the previously proposed canonical model for the dissociation of eIF4E from 4E-BP1, wherein higher-order phosphorylations are entirely predicated upon priming phosphorylations at Thr-37 and Thr-46, these priming phosphorylations are not required for 4E-BP1 hyperphosphorylation during mitosis because CDK1/cyclin B can substitute for mTOR to phosphorylate 4E-BP1 at multiple sites ( xref )."
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"4E-BP1 is a downstream target of the Akt-mTOR (mammalian target of rapamycin) signaling pathway : When 4E-BP1 is hyperphosphorylated by mTOR, it releases the protein translation initiation factor eIF4E, thereby allowing eIF4E to bind to 7-methyl guanosine capped messenger RNA and to recruit the ribosomal machinery required for translation."
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"Both pathways enable mTOR to carry out kinase activity by directly phosphorylating 4E-BP1 and ribosomal protein S6 kinase 1 (p70S6k), thus initiating the eukaryotic translation via phosphorylations of S6 and eIF4 (Follo et al., 2019; Shi et al., 2019; Yoder et al., 2019; Iffland et al., 2020)."
sparser
"Recent findings suggest that the two proteins known to function downstream of mammalian mTOR (p70S6K and PHAS-I) may represent two distinct signaling pathways, because the phosphorylation of PHAS-I by mTOR is still rapamycin sensitive in cells expressing a rapamycin-resistant form of p70S6K [ xref ]."
sparser
"SESN2 inhibits mTOR-dependent phosphorylation of p70S6K and 4E-BP1,( xref )and knockdown of SESN2 resulted in the activation of mTOR signaling indicating that the important role of SESN2 on mTOR inhibition.( xref )Our results from western blotting demonstrated that mTOR was down-regulated by fisetin treatment in HNCCs consistent with other previous studies showing tumor inhibiting potentials of fisetin through mTOR pathway.( xref , xref , xref )These results suggest that fisetin-induced apoptotic potentials is through SESN2/mTOR signaling axis."
sparser
"While some studies suggest that mitotic and/or CDK1-dependent phosphorylation of 4EBP1 replaces mTOR-dependent phosphorylation of 4EBP1 during mitosis ( xref ; xref ) and thus relieves the inhibitory effect of 4EBP1 on cap-dependent translation; others ( xref , xref ) do not observe a measurable difference in cap-dependent translation in the presence or absence of mitotic 4EBP1 phosphorylation, which is characterized by an additional phosphorylation event on S83."
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"ROS triggered PI3K activation can transduce oncogenic AKT-mTOR signaling; mTOR can increase the phosphorylation of both eukaryotic initiation factor 4E binding protein1 (4EBP-1) and S6K1, leading to the translation and expression of mRNAs encoding several major anti-apoptotic proteins including XIAP, c-IAP1, Bcl-XL, and BCl-2 [XREF_BIBR]."
sparser
"To promote this type of translation, eukaryotic translation initiation factor 4E (eIF4E) has to bind with eIF4A and eIF4G, creating multisubunit eIF4F. By mTOR phosphorylation of 4E-binding protein 1 (4E-BP1), it releases eIF4E, allowing it to start the cap-dependent translation."
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"Recent findings suggest that the two proteins known to function downstream of mammalian mTOR (p70S6K and PHAS-I) may represent two distinct signaling pathways, because the phosphorylation of PHAS-I by mTOR is still rapamycin sensitive in cells expressing a rapamycin resistant form of p70S6K [XREF_BIBR]."
sparser
"Since mTOR phosphorylates 4EBP1, resulting in its dissociation from eIF4E and leading to the formation of the translation initiation complex xref , we used mutant 4EBP1-5A, which lacks the five Ser/Thr phosphorylation sites targeted by mTOR and thus acts as a dominant negative inhibitor by binding elF4E to prevent translation initiation xref ."
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"Phospho-4E-BP1 expression was reduced after treatment (mean -2.3; range -6 to +1; p < 0.001), suggesting a reduction in mTOR dependent phosphorylation of 4E-BP1, but this reduction in phospho-4E-BP1 was not significantly correlated with the reduction in estimated eIF4E activity, and changes in levels of the other components had strong influences on estimated eIF4E activity."
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"In addition, CD40 ligation was found to mediate a PI3K- and mammalian target of rapamycin (mTOR)-dependent phosphorylation of 4E-BP1 and its subsequent dissociation from the mRNA cap binding protein eIF4E as well as an ERK dependent phosphorylation of eIF4E, thus promoting translation initiation."
sparser
"Phosphorylation of S6K1 on Thr390 (human Thr389) is a primary activator of its kinase activity and appears to regulate translation of ribosome-related transcripts and ribosome biogenesis, although the mechanism underlying differential regulation of phosphorylation of Eif4ebp1 and S6K1 by Frap1 is currently unknown xref ."
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"p70 S6K phosphorylates the ribosomal protein S6 (rpS6), resulting in increased translation of mRNAs containing a 5 ' olygopyrimidine tract, whereas phosphorylation of 4E-BP1 by mTOR relieves inhibition on the initiation factor eIF4E resulting in more efficient cap dependent translation XREF_BIBR."
reach
"One of the most important effector molecules downstream of PI3K and Akt pathway appears to be the mammalian target of rapamycin (mTOR), a key regulator of protein synthesis, which can subsequently phosphorylate S6 kinase (S6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1)."
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"Most cellular stress conditions block eIF4E activity by suppressing mTOR dependent phosphorylation of 4EBP1, which is thought to be mediated by AMP activated protein kinase (AMPK)-dependent activation of the mTOR inhibitor TSC2 (also known as tuberin) 168, although REDD1 (also known as DDIT4) and RAS GTPases, respectively, have also been implicated in mTOR control during hypoxia and amino acid deprivation XREF_BIBR, XREF_BIBR."
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"The mTOR pathway, a significant controlling factor for MPS, stimulates the kinase activity of the complex and leads to the phosphorylation of 4E-BP1 and p70S6K, which are two enzymes that also modulate protein synthesis at the level of mRNA translation initiation [XREF_BIBR, XREF_BIBR]."
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"The immunohistochemical expression of mTOR related proteins tuberous sclerosis complex 2 (TSC2), phosphatase and tensin homologue (PTEN), phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (p-4EBP1), phosphorylated mTOR (p-mTOR), and phosphorylated ribosomal protein S6 kinase B1 (p-P70S6K) were analyzed using Image-Pro Plus software."
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"We found that overexpression of 4EBP1 promoted the apoptosis rate as well as the VP1 expression after viral infection, and overexpression of p70S6K promoted apoptosis while decreased the VP1 expression at 24h p. i. Activated mTOR phosphorylates the downstream effectors 4EBP1 and p70S6K."
sparser
"Under the condition of stimuli, PI3K phosphorylates PIP2 to create PIP3 and recruits AKT to the plasma membrane to active PDK1 and mTOR complex which phosphorylates 4E-BP1 and p70 ribosomal S6 kinase that trigger ribosome biogenesis and translation in cell growth and division [ xref , xref ] ( Figs. xref & xref )."
reach
"The phosphorylation of 4EBP1 by mTOR in response to growth factor and nutrient status causes it to dissociate from eIF4E allowing eIF4G and associated factors to bind to the 5 ' cap, recruit the 40S subunit of the ribosome, and scan the mRNA for the start codon to initiate translation."
sparser
"Even though Rh30 and RD cells are p53-negative; knockdown of NR4A1 in Rh30 cells or treatment with DIM-C-pPhOH induced sestrin 2 and increased phosphorylation of AMPKα and this resulted in decreased activation of mTOR-dependent phosphorylation of both 4EBP1 and 6SRP which are kinases downstream from mTOR (Figure xref )."
rlimsp
"Since mTOR phosphorylates 4EBP1, resulting in its dissociation from eIF4E and leading to the formation of the translation initiation complex [29], we used mutant 4EBP1-5A, which lacks the five Ser/Thr phosphorylation sites targeted by mTOR and thus acts as a dominant negative inhibitor by binding elF4E to prevent translation initiation [30]."
sparser
"Another point of convergence of the PIM and PI3K pathways is mTOR, a molecule downstream of PI3K that is responsible for cellular processes, including cell survival and protein synthesis, and influences the pathogenesis of disorders such as cancer and type 2 diabetes. xref , xref Both PIM and AKT negatively regulate mTOR by phosphorylation of PRAS40 (proline-rich Akt substrate of 40 kDa) xref and TSC2 (tuberous sclerosis complex 2), xref the latter of which occurs by both directly and indirectly decreasing AMPK (5' adenosine monophosphate-activated protein kinase) activation. xref Moreover, mTOR and PIM can phosphorylate 4E-BP1 to allow for protein translation and MYC signaling. xref Another link between the pathways is the phosphorylation of c-MYC, which prevents apoptosis and allows the oncogene to drive tumorigenesis. xref , xref , xref , xref "
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"The effect of androgens on translation is mediated through several mechanisms including changes in miRNA expression or processing XREF_BIBR - XREF_BIBR, phosphorylation of translation factors like eEF2 XREF_BIBR, or mTOR activation mediated phosphorylation of p70S6 and 4E-BP1 XREF_BIBR."
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"In addition, mTOR, another substrate subjected to phosphorylation by Akt, enhances phosphorylation of S6K1 and 4E-BP1 and plays a crucial role in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both the transcriptional and translational levels XREF_BIBR."
sparser
"By contrast, LY294002, a direct inhibitor of many PI3K family members including mTOR, was equally effective at inhibiting the phosphorylation of S6K and 4EBP1 by mTOR in vitro [ xref ] and in cells [ xref ], although this finding is complicated by LY294002′s inhibition of multiple lipid and protein kinases [ xref ] including PIM, a kinase potentially upstream of 4EBP1 phosphorylation [ xref , xref ]."
sparser
"Additionally, mTOR phosphorylates the eukaryotic initiation factor 4E binding protein-1 (4E-BP1), a protein that binds to and inhibits activity of the eukaryotic initiation factor eIF4E. When 4E-BP1 is phosphorylated by mTOR, it dissociates from eIF4E, allowing eIF4E to complex with other initiation factors to initiate mRNA translation."
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"Pre-treatment with LY294002, an inhibitor of PI3K, or with MK2206, an inhibitor of AKT (XREF_SUPPLEMENTARY), or with rapamycin or RAD001 (XREF_SUPPLEMENTARY), the inhibitor of mTOR, blocked the phosphorylation of 4E-BP1 mediated by the PI3K and AKT pathway, and disrupted upregulation of USP15 synthesis mediated by TGF-beta (XREF_FIG)."
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"AZD8055 (XREF_FIG) is a prototypic, orally-available, ATP-competitive mTOR kinase inhibitor, that suppresses phosphorylation of the mTORC1 substrates p70S6K and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), as well as phosphorylation of the mTORC2 substrate AKT (S473)."
sparser
"Moreover, although phosphorylation of conventional mTOR sites in 4E-BP1 decreased during contraction, mTOR-independent phosphorylation was also apparent, which was associated with the release of 4E-BP1 from eIF4E. The results indicate mTOR-independent phosphorylation of S6K1 and 4E-BP1 and suggest MEK/ERK/RSK1-dependent phosphorylation of eIF4B during skeletal muscle contraction."
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"MTOR is then activated as a kinase and can phosphorylate p70-S6 kinase, which then phosphorylates downstream targets like S6 (to form phosphorylated S6, or phospho-S6) and the eukaryotic initiation factor 4E (4EBP1, to form phospho-4EBP1) that increase protein translation and also activate mTOR activity by a positive feedback loop."
sparser
"When activated, mTOR phosphorylates S6K and 4E-BP1 to promote protein translation and is sensitive to rapamycin inhibition.[ xref ] Recent studies have shown that mTOR may regulate T-cell differentiation and adaptive immunity following the binding of the T-cell receptor to antigen.[ xref ] In preliminary experiments, we found that mTOR modulates lymphocyte differentiation in immunosuppressed animals with fungal infections by regulating the transcription factors T-box expressed in T-cells (T-bet) and eomesodermin.[ xref ] T-bet is a key transcription factor regulating T-cell differentiation and belongs to the T-box transcription factor family.[ xref ] Eomesodermin plays a synergistic role in T-bet function and regulates the differentiation of CD8 + T-cells into effector and memory T-cells."
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"Inhibition of mTOR decreases phosphorylation of two downstream targets, 4E-BP1 and S6K, resulting in inhibition of protein synthesis [XREF_BIBR], which does not necessarily induce apoptosis, but it can be considered in combination with other drugs as it induces cell arrest and sensitizes cells to apoptosis [XREF_BIBR]."
| PMC
sparser
"In addition, mTOR, another substrate subjected to phosphorylation by Akt, enhances phosphorylation of S6K1 and 4E-BP1 and plays a crucial role in the regulation of ribosomal protein synthesis, for example, production of cyclin D1 and VEGF-A at both the transcriptional and translational levels xref ."
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"Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by the mTOR and raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR regulated sites."
reach
"Phosphorylation of 4E-BP1 by mammalian target of rapamycin (mTOR), AKT, and extracellular signal–regulated kinase (ERK) prevents 4E-BP1 binding to the eIF-complex, leading to an aberrantly upregulated translational efficiency, which is an important characteristic of tumor growth, metastatic progression, and cancer stem cell enrichment [7,8]."
sparser
"In addition, mTOR phosphorylates and inactivates eukaryotic initiation factor 4E-BP1, resulting in the release of inhibition on eIF4E, and promotes translation initiation.[ xref ] To confirm the role of the IGF-1/IGF-1R axis in the CD26-regulating pathway, the IGF-1Rs in CD26 − and CD26 + KFs were knocked down; the results revealed that stably silenced IGF-1Rs in CD26 − KFs (CD26 − /sh-IGF1R) and CD26 + KFs (CD26 + /sh-IGF1R) were established ( xref )."
sparser
"It was recently reported that protein-binding function of PKR promotes the proliferation of pancreatic β cells through TNF receptor-associated factor 2 (TRAF2)/receptor-interacting protein 1 (RIP1)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B)/c-Myc pathway [ xref ], while cancer cell survival requires mTOR-dependent phosphorylation of 4EBP1 in Myc-dependent tumor, and PP2A-B56 α holoenzyme can negatively regulate c-Myc protein accumulation [ xref , xref ]."
rlimsp
"Geldanamycin, a potent inhibitor of Hsp90, disrupted the in vivo binding of Hsp90 to raptor without affecting the association of raptor and mTOR, and suppressed the phosphorylation by mTOR of the downstream translational regulators p70 S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1)."
reach
"By contrast, LY294002, a direct inhibitor of many PI3K family members including mTOR, was equally effective at inhibiting the phosphorylation of S6K and 4EBP1 by mTOR in vitro [XREF_BIBR] and in cells [XREF_BIBR], although this finding is complicated by LY294002 's inhibition of multiple lipid and protein kinases [XREF_BIBR] including PIM, a kinase potentially upstream of 4EBP1 phosphorylation [XREF_BIBR, XREF_BIBR]."
sparser
"Phospho-4E-BP1 expression was reduced after treatment (mean -2.3; range -6 to +1; p < 0.001), suggesting a reduction in mTOR-dependent phosphorylation of 4E-BP1, but this reduction in phospho-4E-BP1 was not significantly correlated with the reduction in estimated eIF4E activity, and changes in levels of the other components had strong influences on estimated eIF4E activity."
sparser
"Phosphorylation of 4E-BP1 by mammalian target of rapamycin (mTOR), AKT, and extracellular signal–regulated kinase (ERK) prevents 4E-BP1 binding to the eIF-complex, leading to an aberrantly upregulated translational efficiency, which is an important characteristic of tumor growth, metastatic progression, and cancer stem cell enrichment [ xref , xref ]."
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"As described in the Introduction, mTOR dependent increases in 4E-BP1 phosphorylation can lead to the dissociation of 4E-BP1 from eIF4E while simultaneously enhancing the association of eIF4E with eIF4G (i.e. the formation of eIF4F complex, which is crucial for the cap dependent initiation of translation)."
sparser
"This observation raises the possibility that kinases other than mTOR may phosphorylate 4E-BP1 in SCC cells, including members of the MAP kinase (MAPKs) and cyclin-dependent kinase (CDK) superfamily, as previously reported ( xref - xref ), which may account for the rapamycin insensitivity of the phosphorylation of 4E-BP1."
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"While p70S6K phosphorylation at Thr389 is required for its activity and is blocked by rapamycin, 4E-BP1 is phosphorylated on multiple sites by mTOR, and it is the largely rapamycin-insensitive phosphorylation of Thr46 that prevents inhibitory binding to the 5 ' mRNA cap binding protein eIF4E [XREF_BIBR, XREF_BIBR]."
reach
"Even though Rh30 and RD cells are p53 negative; knockdown of NR4A1 in Rh30 cells or treatment with DIM-C-pPhOH induced sestrin 2 and increased phosphorylation of AMPKalpha and this resulted in decreased activation of mTOR dependent phosphorylation of both 4EBP1 and 6SRP which are kinases downstream from mTOR."
sparser
"Most cellular stress conditions block eIF4E activity by suppressing mTOR-dependent phosphorylation of 4EBP1, which is thought to be mediated by AMP-activated protein kinase (AMPK)-dependent activation of the mTOR inhibitor TSC2 (also known as tuberin) xref , although REDD1 (also known as DDIT4) and RAS GTPases, respectively, have also been implicated in mTOR control during hypoxia and amino acid deprivation xref , xref ."
reach
"In human prostate cancer cells, constitutive expression of HIF-1alpha was found to require signal transduction via phosphatidylinositol-3-kinase (PI3K), AKT (protein kinase B), and the mammalian target of rapamycin (mTOR; also known as FKBP and rapamycin binding protein), a serine/threonine protein kinase that phosphorylates p70 ribosomal protein S6 kinase 1 (S6K1) and the eIF-4E binding protein 1 (4E-BP1), thereby stimulating protein synthesis."
sparser
"Besides this, activation of mTOR by AKT can phosphorylate and inactivate 4E-BP1 (for eIF4E-Binding Proteins), a family of small acidic proteins that function as translational repressors of eIF4E. Phosphorylation of 4E-BP1 by mTOR releases 4E-BP1 from eIF4E thereby activating eIF4E involved translation-initiation complex and consequently the translational repertoire of a cell toward malignancy [ xref ]."
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"Overall, these data suggest that the upregulation of TCTP during mechanical overload induced muscle growth occurs via both a rapamycin-insensitive mechanism (possibly mTOR mediated phosphorylation of 4E-BP1) and a rapamycin sensitive mTOR kinase dependent mechanism (e.g., p70 S6K1 and/or eIF4G phosphorylation)."
sparser
"We hypothesized that mechanism by which rapamycin induced the up-regulation of HSPs in PDAPP brains may involve rapamycin-induced inhibition of 4E-BP1 phosphorylation by mTOR, which would in turn inhibit cap-dependent protein synthesis and thus allow for the preferential translation of pre-existing HSP mRNAs ( xref ; xref ; xref )."
rlimsp
"We found that overexpression of 4EBP1 promoted the apoptosis rate as well as the VP1 expression after viral infection, and overexpression of p70S6K promoted apoptosis while decreased the VP1 expression at 24 h p. i. Activated mTOR phosphorylates the downstream effectors 4EBP1 and p70S6K."
sparser
"Activated mTOR phosphorylates the downstream effectors 4EBP1 and p70S6K. Being responsible for the cap-dependent translation of mRNA and the protein synthesis, they are critical components in a pathway regularly co-opted by viruses to ensure translation of their own mRNA. xref , xref Our previous work has shown that CVB3 infection can activate mTOR/4EBP1 pathway to promote the synthesis and release of the viral protein. xref In this study, CVB3 infection directly stimulated PI3K/Akt pathway, keeping the mTOR/4EBP1 pathway activating."
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"On the basis of high-throughput bioavailability studies of brain bioavailable metabolites after dietary BDPP treatment, we found that select polyphenol metabolites [e.g., cyanidin-3 '- O-glucoside and 3-(3 '-hydroxyphenyl) propionic acid] were able to rescue mTOR and p70S6K phosphorylation in primary cortico-hippocampal neuronal cultures, as well as rescue 4E-BP1 phosphorylation in response to treatment with 4EGI-1, a specific inhibitor of eIF4E-eIF4G interaction."
sparser
"In addition, CD40 ligation was found to mediate a PI3K- and mammalian target of rapamycin (mTOR)-dependent phosphorylation of 4E-BP1 and its subsequent dissociation from the mRNA cap-binding protein eIF4E as well as an ERK-dependent phosphorylation of eIF4E, thus promoting translation initiation."