Ser-64 and Ser-111 in PHAS-I Are Dispensable for Insulin-stimulated Dissociation from eIF4E

Ferguson, Gail; Mothe-Satney, Isabelle; Lawrence, John C.

doi:10.1074/jbc.m307949200

Cited by 27 publications

(24 citation statements)

References 36 publications

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“…Recently, several reports have shown that p53 is able to induce or activate novel protein phosphatases (Li et al, 2003;Ueda et al, 2003;Yin et al, 2003) but whether any of these act on 4E-BP1 remains to be established. It may be significant that the greatest p53-induced loss of phosphate from 4E-BP1 in vivo appears to involve Ser 64 , since this site can have a large influence on the binding of the protein to eIF4E (Mothe-Satney et al, 2000b;Karim et al, 2001) (although this conclusion has been challenged; Ferguson et al, 2003). 4E-BP1 is phosphorylated in a hierarchical fashion, with Ser 64 being the last site to be modified when cells are stimulated by serum (Gingras et al, 1999a(Gingras et al, , 2001a.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the phosphorylation and integrity of protein synthesis initiation factor eIF4GI and the translational repressor 4E-BP1 by p53

Constantinou

Clemens

2005

Oncogene

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Activation of a temperature-sensitive form of mouse p53 in murine erythroleukaemia cells rapidly inhibits protein synthesis and causes early dephosphorylation and cleavage of protein synthesis initiation factor eIF4GI and the eIF4E-binding protein 4E-BP1. Dephosphorylated 4E-BP1 and the cleaved products of 4E-BP1 and eIF4GI associate with eIF4E under these conditions, concomitant with decreased interaction of full-length eIF4GI with eIF4E. These changes may play an important role in preventing formation of the eIF4F complex and thus the initiation of protein synthesis. As observed previously for eIF4GI, the cleavage of 4E-BP1 is insensitive to the general caspase inhibitor z-VAD.FMK, consistent with a caspase-independent mechanism of factor modification and regulation of protein synthesis. Comparison of the p53-induced patterns of eIF4GI and 4E-BP1 dephosphorylation and cleavage with those caused by the mTOR inhibitor rapamycin indicates that p53 activation and rapamycin have distinct but additive effects. Moreover, p53 activation inhibits rapamycin-insensitive protein kinase activity against 4E-BP1. P53 and rapamycin have additive effects on the inhibition of overall protein synthesis. These data suggest that the inhibition of protein synthesis by p53 is largely independent of the regulation of rapamycin-sensitive mTOR in the system under investigation.

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Section: Discussionmentioning

confidence: 99%

Regulation of the phosphorylation and integrity of protein synthesis initiation factor eIF4GI and the translational repressor 4E-BP1 by p53

Constantinou

Clemens

2005

Oncogene

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“…In HEK 293 cells, for example, their phosphorylation is dependent upon the C-terminal TOS motif . Although there are data that suggest that phosphorylation of this site is required for release of eIF4E from 4E-BP1, the role of phosphorylation of Ser65 is still controversial (Ferguson et al, 2003). Molecular dynamics findings (Tomoo et al, 2005) and earlier biophysical data suggest that phosphorylation of Ser65 and Thr70 is insufficient to bring about release from eIF4E.…”

Section: Control Of the 4e-bps By Mtormentioning

confidence: 99%

When translation meets transformation: the mTOR story

2006

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“…Akt and mTOR-dependent phosphorylation of Thr37,46 may be the priming event ( Figure 5) (42) that leads to phosphorylation of Thr70 and Ser65; phosphorylation at these four sites may be enough to release eIF4E (70). Some suggest that phosphorylation at Ser65 and Ser111 may not be needed for release of eIF4E (71). Other kinases, such as cdc 2 and ataxia telangiectasia mutated, may act as kinases for 4E-BP1 (72,73).…”

Section: Signaling Regulation Of Mrna Translationmentioning

confidence: 99%

mRNA Translation

Kasinath

Mariappan²,

Sataranatarajan³

et al. 2006

Journal of the American Society of Nephrology

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Ambient protein levels are under coordinated control of transcription, mRNA translation, and degradation. Whereas transcription and degradation mechanisms have been studied in depth in renal science, the role of mRNA translation, the process by which peptide synthesis occurs according to the genetic code that is present in the mRNA, has not received much attention. mRNA translation occurs in three phases: Initiation, elongation, and termination. Each phase is controlled by unique eukaryotic factors. In the initiation phase, mRNA and ribosomal subunits are brought together. During the elongation phase, amino acids are added to the nascent peptide chain in accordance with codon sequences in the mRNA. During the termination phase, the fully synthesized peptide is released from the ribosome for posttranslational processing. Signaling pathways figure prominently in regulation of mRNA translation, particularly the phosphatidylinositol 3 kinase-Akt-mammalian target of rapamycin pathway, the AMP-activated protein kinase-tuberous sclerosis complex protein 1/tuberous sclerosis complex protein 2-Rheb pathway, and the extracellular signal-regulated kinase 1/2 type mitogen-activated protein kinase signaling pathway; there is significant cross-talk among these pathways. Regulation by mRNA translation is suggested when changes in mRNA and protein levels do not correlate and in the setting of rapid protein synthesis. Ongoing work suggests an important role for mRNA translation in compensatory renal growth, hypertrophy and extracellular matrix synthesis in diabetic nephropathy, growth factor synthesis by kidney cells, and glomerulonephritis. Considering that mRNA translation plays an important role in cell growth, development, malignancy, apoptosis, and response to stress, its study should provide novel insights in renal physiology and pathology.

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Ser-64 and Ser-111 in PHAS-I Are Dispensable for Insulin-stimulated Dissociation from eIF4E

Cited by 27 publications

References 36 publications

Regulation of the phosphorylation and integrity of protein synthesis initiation factor eIF4GI and the translational repressor 4E-BP1 by p53

Regulation of the phosphorylation and integrity of protein synthesis initiation factor eIF4GI and the translational repressor 4E-BP1 by p53

When translation meets transformation: the mTOR story

mRNA Translation

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