β-Catenin is O-GlcNAc glycosylated at Serine 23: Implications for β-catenin's subcellular localization and transactivator function

Ha, Jacqueline R.; Li, Hao; Venkateswaran, Geetha; Huang, Yuhao; Garcia, Elizabeth; Persad, Sujata

doi:10.1016/j.yexcr.2013.11.021

Cited by 48 publications

(35 citation statements)

References 29 publications

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“…Many factors that regulate brown adipocyte differentiation, such as PGC1α [29], PPARγ [30] and β-catenin [31], have been identified. Importantly, these factors were O-GlcNAcylated [12,32,33]. Thus, we speculate that the increased brown adipocyte differentiation in Oga +/-mice might be due to the altered activity of key factors that are O-GlcNAcylated or form complexes with O-GlcNAc cycling enzymes.…”

Section: Discussionmentioning

confidence: 90%

Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga +/- mice

et al. 2015

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Aims/hypothesis O-GlcNAcylation plays a role as a metabolic sensor regulating cellular signalling, transcription and metabolism. Transcription factors and signalling pathways related to metabolism are modulated by N-acetyl-glucosamine (OGlcNAc) modification. Aberrant regulation of OGlcNAcylation is closely linked to insulin resistance, type 2 diabetes and obesity. Current evidence shows that increased O-GlcNAcylation negatively regulates insulin signalling, which is associated with insulin resistance and type 2 diabetes. Here, we aimed to evaluate the effects of Oga (also known as Mgea5) haploinsufficiency, which causes hyper-OGlcNAcylation, on metabolism. Methods We examined whether Oga +/-mice developed insulin resistance. Metabolic variables were determined including body weight, glucose and insulin tolerance, metabolic rate and thermogenesis. Results Oga deficiency does not affect insulin signalling even at hyper-O-GlcNAc levels. Oga +/-mice are lean with reduced fat mass and improved glucose tolerance. Furthermore, Oga +/-mice resist high-fat diet-induced obesity with ameliorated hepatic steatosis and improved glucose metabolism. Oga haploinsufficiency potentiates energy expenditure through the enhancement of brown adipocyte differentiation from the stromal vascular fraction of subcutaneous white adipose tissue (WAT). Conclusions/interpretation Our observations suggest that O-GlcNAcase (OGA) is essential for energy metabolism via regulation of the thermogenic WAT program.

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Section: Discussionmentioning

confidence: 90%

Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga +/- mice

et al. 2015

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“…58 Moreover, Ser23 glycosylation is likely required for the transcription and cell proliferation effects of increased global O-GlcNAc levels in this system, because a Ser23Gly β -catenin mutant was unable to effect these responses. 58 Interestingly, O-GlcNAcylation may be a more general mode of regulating β -catenin interactions, because the Lefebvre group demonstrated that glycosylation of β -catenin stabilizes it in human colon cell lines and promotes its interaction with α -catenin, forming an adherens junction subcomplex required for the integrity of mucosa. 59 Whether β -catenin glycosylation directly promotes E-cadherin and/or α -catenin binding and how this is accomplished remains to be determined.…”

Section: Protein–protein Interactions Induced By O-glcnacmentioning

confidence: 95%

A Sweet Embrace: Control of Protein–Protein Interactions by O-Linked β-N-Acetylglucosamine

2017

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O-Linked β-N-acetylglucosamine (O-GlcNAc) is a critical post-translational modification (PTM) of thousands of intracellular proteins. Reversible O-GlcNAcylation governs many aspects of cell physiology and is dysregulated in numerous human diseases. Despite this broad pathophysiological significance, major aspects of O-GlcNAc signaling remain poorly understood, including the biochemical mechanisms through which O-GlcNAc transduces information. Recent work from many laboratories, including our own, has revealed that O-GlcNAc, like other intracellular PTMs, can control its substrates’ functions by inhibiting or inducing protein–protein interactions. This dynamic regulation of multiprotein complexes exerts diverse downstream signaling effects in a range of processes, cell types, and organisms. Here, we review the literature about O-GlcNAc-regulated protein–protein interactions and suggest important questions for future studies in the field.

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“…Upon glycosylation of SER 23 , β-catenin undergoes translocation from the cell nucleus to cell membranes. This is linked to amplification of β-catenin interaction with E-cadherin, a decreased β-catenin-TCF interaction, decreased transcriptional activity and Wnt target gene expression [39].…”

Section: Receptors Of Frizzled Familymentioning

confidence: 99%

Alterations of Wnt/β-catenin signaling pathway in hepatocellular carcinomas associated with hepatitis C virus

Rogacki¹,

Kasprzak²,

Stępiński³

2015

pjp

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β-Catenin is O-GlcNAc glycosylated at Serine 23: Implications for β-catenin's subcellular localization and transactivator function

Cited by 48 publications

References 29 publications

Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga +/- mice

Obesity resistance and increased energy expenditure by white adipose tissue browning in Oga +/- mice

A Sweet Embrace: Control of Protein–Protein Interactions by O-Linked β-N-Acetylglucosamine

Alterations of Wnt/β-catenin signaling pathway in hepatocellular carcinomas associated with hepatitis C virus

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