eIF3f depletion impedes mouse embryonic development, reduces adult skeletal muscle mass and amplifies muscle loss during disuse

Docquier, Aurélie; Pavlin, Laura; Raibon, Audrey; Bertrand‐Gaday, Christelle; Sar, Chamroeun; Leibovitch, Serge A.; Candau, Robin; Bernardi, Henri

doi:10.1113/jp277841

Cited by 19 publications

(18 citation statements)

References 78 publications

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“…There is a dephosphorylated S6K downstream of the mTORC1 pathway, which is located on the eIF3 scaffold complex. Active mTORC1 is recruited onto the eIF3 scaffold and then phosphorylates S6K to activate it [28]. The mTORC1 phosphorylates at least two amino acid residues of S6K1, of which the most critical modification is located on the threonine residue (T389) [29].S6K1 activity can be determined by activating S6 ribosomal protein (phospo-S6 ribosomal protein, p-S6) and eIF4B, and the level of P-S6 in the body can be used as an indicator of the activation degree of the mTORC1 pathway [30].…”

Section: Discussionmentioning

confidence: 99%

The expression and significance of mTORC1 in diabetic retinopathy

Zheng

Zhou

et al. 2020

BMC Ophthalmol

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Background: To investigate the expression and significance of mechanistic target of rapamycin complex 1(mTORC1) in diabetic retinopathy (DR), and to find new targets and new methods for the treatment of DR. Methods: A DR rat model was prepared by general feeding combined with intraperitoneal injection of 10% streptozotocin (60 mg/kg). The rats were randomly divided into a control group (NDM group) and a diabetes group (DM group). Three months later, the degrees of retinopathy was determined using hematoxylin and eosin staining, and the levels of p-S6, VEGF, and PEDF proteins were detected by immunohistochemistry and western blotting. Human retinal capillary endothelial cells (HRCECs) were cultured in high glucose (HG) conditions, then treated with rapamycin or transfected with siTSC1.The protein levels of p-S6 were assessed by western blotting. The 5-ethynyl-2′deoxyuridine assay was used to detect cell proliferation, and the Transwell assay was used to detect cell migration. Results: A DM rat model was successfully developed. The expressions of p-S6 and VEGF proteins were significantly increased in the DM group (p < 0.05), and the expression of PEDF protein was significantly decreased compared with the NDM group (p < 0.05). In vitro, the p-S6 protein, as well as cell proliferation and migration, in HG induced HRCECs were increased (p < 0.05) compared with the control (normal glucose) group (p < 0.05). After transfection with siTSC1 to activate mTORC1, the expression of p-S6, as well as cell proliferation and migration, were increased. In contrast, rapamycin decreased p-S6 expression, as well as proliferation and migration, in HG induced HRCECs compared to the control group (p < 0.05). Conclusion: mTORC1 plays an important role in DR. After activation, mTORC1 induced expression of the p-S6 protein, regulated the expressions of VEGF and PEDF proteins, and changed the proliferation and migration of endothelial cells. The mTORC1 can therefore be used as a new target,as well as in the treatment of DR.

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Section: Discussionmentioning

confidence: 99%

The expression and significance of mTORC1 in diabetic retinopathy

Zheng

Zhou

et al. 2020

BMC Ophthalmol

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“…Starvation muscle atrophy is suppressed when an eIF3f mutant insensitive to polyubiquitination by MAFbx is overexpressed, showing its critical role in muscle homeostasis during such a stress [74]. More recently, eIF3f was found to be essential for mouse embryonic development and its partial depletion reduces adult skeletal mass and amplifies muscle loss during disuse by mainly modulating protein synthesis [75]. Concerning exercise, an increase of eIF3f expression was evidenced during overload [70], suggesting a role in adaptations to exercise.…”

Section: Ampk and Mtorc1 Pathwaysmentioning

confidence: 99%

Recent Data on Cellular Component Turnover: Focus on Adaptations to Physical Exercise

Sanchez

Candau

Bernardi³

2019

Cells

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Significant progress has expanded our knowledge of the signaling pathways coordinating muscle protein turnover during various conditions including exercise. In this manuscript, the multiple mechanisms that govern the turnover of cellular components are reviewed, and their overall roles in adaptations to exercise training are discussed. Recent studies have highlighted the central role of the energy sensor (AMP)-activated protein kinase (AMPK), forkhead box class O subfamily protein (FOXO) transcription factors and the kinase mechanistic (or mammalian) target of rapamycin complex (MTOR) in the regulation of autophagy for organelle maintenance during exercise. A new cellular trafficking involving the lysosome was also revealed for full activation of MTOR and protein synthesis during recovery. Other emerging candidates have been found to be relevant in organelle turnover, especially Parkin and the mitochondrial E3 ubiquitin protein ligase (Mul1) pathways for mitochondrial turnover, and the glycerolipids diacylglycerol (DAG) for protein translation and FOXO regulation. Recent experiments with autophagy and mitophagy flux assessment have also provided important insights concerning mitochondrial turnover during ageing and chronic exercise. However, data in humans are often controversial and further investigations are needed to clarify the involvement of autophagy in exercise performed with additional stresses, such as hypoxia, and to understand the influence of exercise modality. Improving our knowledge of these pathways should help develop therapeutic ways to counteract muscle disorders in pathological conditions.

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“…29 Notably, eIF3f regulates skeletal muscle size through interaction with the mTOR/raptor complex, thereby promoting the phosphorylation of S6K1 and regulating downstream effectors of mTOR. [30][31][32] eIF3f has also been reported to play roles in various cancers. Most investigations have shown that eIF3f acts as a tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

<p>Targeting eIF3f Suppresses the Growth of Prostate Cancer Cells by Inhibiting Akt Signaling</p>

Li¹,

Yu²,

Ge³

et al. 2020

OTT

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Background: Eukaryotic initiation factor 3 (eIF3) is the largest translation initiation factor, and oncogenic roles have been discovered for its subunits, including the f subunit (ie, eIF3f), in various human cancers. However, the roles of eIF3f in the development and progression of prostate cancer (PCa) have not been reported. Materials and Methods: We performed in silico analysis to screen the expression of eIF3 subunits. Relevant shRNAs were used to knock down eIF3 subunits in 22Rv1 cells and cell proliferation was analyzed. eIF3f expression in PCa specimens was confirmed by immunohistochemistry. eIF3f knockdown was established to evaluate the effects of eIF3f on cell proliferation in vitro and in vivo. RNA-seq, bioinformatics analysis and Western blotting were applied to explore the molecular details underlying the biological function of eIF3f in PCa cells. shRNA-resistant eIF3f and myristoylated-Akt were used to rescue the effects of eIF3f disturbance on PCa cells. Results: Functional analyses confirmed that eIF3f is essential for PCa proliferation. Notably, the expression of eIF3f was found to be elevated in human PCa tissues as well as in PCa cell lines. eIF3f silencing significantly suppressed the growth of PCa cells, both in vitro and in vivo. eIF3f expression was positively correlated with Akt signaling activity in RNA-seq profiles and published prostate cohorts. Knockdown of eIF3f markedly reduced the levels of phosphorylated Akt in PCa cells. Exogenous expression of shRNA-resistant eIF3f in eIF3f knockdown cells restored Akt phosphorylation levels and cell growth. Importantly, rescue experiments revealed that ectopic expression of myristoylated-Akt partially alleviated the suppressive effects of eIF3f disturbance with respect to the growth of PCa cells. Conclusion: These results suggested that eIF3f has an oncogenic role in PCa, mediated at least partially through the regulation of Akt signaling, and that eIF3f represents a potential target for the inhibition of PCa growth and progression.

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eIF3f depletion impedes mouse embryonic development, reduces adult skeletal muscle mass and amplifies muscle loss during disuse

Cited by 19 publications

References 78 publications

The expression and significance of mTORC1 in diabetic retinopathy

The expression and significance of mTORC1 in diabetic retinopathy

Recent Data on Cellular Component Turnover: Focus on Adaptations to Physical Exercise

<p>Targeting eIF3f Suppresses the Growth of Prostate Cancer Cells by Inhibiting Akt Signaling</p>

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