Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified

Fardini, Yann; Pérez-Cervera, Yobana; Camoin, Luc; Pagésy, Patrick; Lefebvre, Tony; Issad, Tarik

doi:10.1016/j.bbrc.2015.04.114

Cited by 25 publications

(14 citation statements)

References 29 publications

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“…Forkhead box other-1 (FoxO1) is a forkhead box family member, able to control the expression of genes involved in the regulation of the cell cycle, in response to oxidative stress and apoptosis. FoxO1 appears to be a highly O -Glc N Acylated, since at least five different residues have been found to be modified by this PTM (Thr317, Ser550, Thr648, Ser654 [ 166 ] and Thr646 [ 180 ]). In addition, upon abnormal O- Glc N Acylation, often observed in chronic hyperglycaemia patients, FoxO1 promotes the transcription of PGC-1α , which in turns interacts with FoxO1, in order to activate the genes involved in hepatic gluconeogenesis, G6Pase and PEPCK , leading to further glucose production and therefore to the enhancement of FoxO1 O- Glc N Acylation [ 181 ].…”

Section: Regulation Of Cell Metabolism By O -Glmentioning

confidence: 99%

“…In addition, upon abnormal O- Glc N Acylation, often observed in chronic hyperglycaemia patients, FoxO1 promotes the transcription of PGC-1α , which in turns interacts with FoxO1, in order to activate the genes involved in hepatic gluconeogenesis, G6Pase and PEPCK , leading to further glucose production and therefore to the enhancement of FoxO1 O- Glc N Acylation [ 181 ]. Although increased FoxO1 O- Glc N Acylation correlates with its increased transcriptional activity, functional studies have indicated that only the mutation of the Thr317 residue slightly reduces FoxO1 transcriptional activity [ 180 ].…”

Section: Regulation Of Cell Metabolism By O -Glmentioning

confidence: 99%

See 1 more Smart Citation

The Nutrient-Sensing Hexosamine Biosynthetic Pathway as the Hub of Cancer Metabolic Rewiring

Chiaradonna

Ricciardiello

Palorini

2018

Cells

119

115

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Alterations in glucose and glutamine utilizing pathways and in fatty acid metabolism are currently considered the most significant and prevalent metabolic changes observed in almost all types of tumors. Glucose, glutamine and fatty acids are the substrates for the hexosamine biosynthetic pathway (HBP). This metabolic pathway generates the “sensing molecule” UDP-N-Acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is the substrate for the enzymes involved in protein N- and O-glycosylation, two important post-translational modifications (PTMs) identified in several proteins localized in the extracellular space, on the cell membrane and in the cytoplasm, nucleus and mitochondria. Since protein glycosylation controls several key aspects of cell physiology, aberrant protein glycosylation has been associated with different human diseases, including cancer. Here we review recent evidence indicating the tight association between the HBP flux and cell metabolism, with particular emphasis on the post-transcriptional and transcriptional mechanisms regulated by the HBP that may cause the metabolic rewiring observed in cancer. We describe the implications of both protein O- and N-glycosylation in cancer cell metabolism and bioenergetics; focusing our attention on the effect of these PTMs on nutrient transport and on the transcriptional regulation and function of cancer-specific metabolic pathways.

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Section: Regulation Of Cell Metabolism By O -Glmentioning

confidence: 99%

Section: Regulation Of Cell Metabolism By O -Glmentioning

confidence: 99%

The Nutrient-Sensing Hexosamine Biosynthetic Pathway as the Hub of Cancer Metabolic Rewiring

Chiaradonna

Ricciardiello

Palorini

2018

Cells

119

115

View full text Add to dashboard Cite

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“…Only the mutation of T317 to alanine could reduce the transcriptional activity of FOXO1 by high glucose, while the mutation of other residues had no such effect (Housley et al 2008). Later, Fardini et al identified a new O-GlcNAcylation site T646 on FOXO1, whereas its mutation fails to impact the FOXO1 O-GlcNAcylation and transcriptional activity, suggesting that O-GlcNAcylated residues remain to be explored (Fardini et al 2015). Housley et al showed that high glucose upregulated mRNA expression of Pepck and G6pc by increasing GlcNAcylation of FOXO1 in the absence of insulin (Housley et al 2008).…”

Section: Foxo1 Methylation and O-glcnacylationmentioning

confidence: 99%

Molecular mechanisms of FOXO1 in adipocyte differentiation

Chen

Lü

Tian

et al. 2019

Journal of Molecular Endocrinology

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Forkhead box-O1 (FOXO1) is a downstream target of AKT and plays crucial roles in cell cycle control, apoptosis, metabolism and adipocyte differentiation. It is thought that FOXO1 affects adipocyte differentiation by regulating lipogenesis and cell cycle. With the deepening in the understanding of this field, it is currently believed that FOXO1 translocation between nuclei and cytoplasm is involved in the regulation of FOXO1 activity, thus affecting adipocyte differentiation. Translocation of FOXO1 depends on its post-translational modifications and interactions with 14-3-3. Based on these modifications and interactions, FOXO1 could regulate lipogenesis through PPARγ and the adipocyte cell cycle through p21 and p27. In this review, we aim to provide a comprehensive FOXO1 regulation network in adipocyte differentiation by linking together distinct functions mentioned above to explain their effects on adipocyte differentiation and to emphasize the regulatory role of FOXO1. In addition, we also focus on the novel findings such as the use of miRNAs in FOXO1 regulation and highlight the improvable issues, such as RNA modifications, for future research in the field.

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“…3, D and E). As OGT is known to be promiscuous in catalyzing adjacent sites (38,39), it is possible that mutating one of the Ser-39, Ser-40, or Ser-42 sites will result in O-GlcNAcylation on adjoining sites. We also noted that Ser-39, Ser-40, and Ser-42 contains a PVS motif that has been identified in half of the O-GlcNAcylation sites (Fig.…”

Section: Discussionmentioning

confidence: 99%