O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities

Ha, Chang-Hoon; Lim, Kihong

doi:10.1016/j.bbrc.2015.09.155

Cited by 9 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sugar nucleotide UDP-GlcNAc serves as a donor for O -GlcNAc addition to nucleocytoplasmic proteins whereas OGA removes the O -GlcNAc group from proteins (Mailleux et al, 2016 ). Numerous studies have demonstrated that O -GlcNAcylation is involved in many fundamental cellular processes, including gene transcription (Ha and Lim, 2015 ), cell signaling (Cassey, 1995 ), and apoptosis (Butkinaree et al, 2008 ). More than those, many transcriptional factors, tumor suppressors, oncogenes, and cell receptors have been found to be tightly associated with O -GlcNAcylation in tumorigenesis (Bond and Hanover, 2015 ; Charoensuksai et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Potential coordination role between O-GlcNAcylation and epigenetics

Cai

Jin

2017

Protein Cell

View full text Add to dashboard Cite

Dynamic changes of the post-translational O-GlcNAc modification (O-GlcNAcylation) are controlled by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and the glycoside hydrolase O-GlcNAcase (OGA) in cells. O-GlcNAcylation often occurs on serine (Ser) and threonine (Thr) residues of the specific substrate proteins via the addition of O-GlcNAc group by OGT. It has been known that O-GlcNAcylation is not only involved in many fundamental cellular processes, but also plays an important role in cancer development through various mechanisms. Recently, accumulating data reveal that O-GlcNAcylation at histones or non-histone proteins can lead to the start of the subsequent biological processes, suggesting that O-GlcNAcylation as ‘protein code’ or ‘histone code’ may provide recognition platforms or executive instructions for subsequent recruitment of proteins to carry out the specific functions. In this review, we summarize the interaction of O-GlcNAcylation and epigenetic changes, introduce recent research findings that link crosstalk between O-GlcNAcylation and epigenetic changes, and speculate on the potential coordination role of O-GlcNAcylation with epigenetic changes in intracellular biological processes.

show abstract

Section: Introductionmentioning

confidence: 99%

Potential coordination role between O-GlcNAcylation and epigenetics

Cai

Jin

2017

Protein Cell

View full text Add to dashboard Cite

show abstract

“…As we confirmed that OGT and REV-ERBα are located in both the cytoplasmic and nuclear compartments (refs. 2 and 17 , Fig. 3 A and B , and SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-eight proteins were less represented in immunoprecipitates from REV-ERB α–depleted cells ( Fig. 4 A ), including several previously identified O-GlcNAcylated proteins with structural, signaling, or transcriptional functions such as histone H2B, the transcription factors SP1 and SP3, HCFC1/VP16-accessory protein, and the protein kinase WNK1 ( 17 , 19 , 20 ). To detect lower expressed putative OGT targets, immunoprecipitates were also resolved by SDS/PAGE and areas of the gel ranging from 50 kDa to 170–200 kDa were analyzed by LC-MS/MS after tryptic digestion ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Top ranking proteins again included HCFC1 and SP3, and interestingly other proteins such as OGT itself, the nuclear receptor coactivator CARM1, and AKT1. Although this approach could also potentially identify proteins with a decreased steady-state level in REV-ERBα−depleted cells or interacting with O-GlcNAcylated proteins, many of them have previously been described as bona fide OGT targets and O-GlcNAcylated polypeptides ( 17 , 21 , 22 ). As an example, both AKT and H2B were similarly expressed in naive and REV-ERBα−depleted cells, suggesting that OGT activity does not affect their stability ( Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex

Berthier

Vinod

Porez

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

SignificanceUsing an interactomic approach, we have identified the nuclear receptor REV-ERBα as a O-GlcNAc transferase (OGT) protein partner. REV-ERBα protects cytoplasmic OGT from proteasomal degradation and facilitates cytosolic and nuclear protein O-GlcNAcylation while REV-ERα ligands decreased cytoplasmic OGT activity. REV-ERBα thus exerts pleiotropic activities through OGT, coordinating signal transduction, epigenomic programming, and transcriptional response in the liver.

show abstract

“…We identified enzymes and mitochondrial proteins in which a link between O- GlcNAcylation and impaired catalytic activity was previously described in diabetes ( 17 , 39 ). The second was transcriptional regulation, in part, through O- GlcNAcylation of transcriptional regulators ( 46 , 47 ). It should be noted that additional mechanisms likely exist, such as an emerging role of metabolic regulation of epigenetics and its impact on gene expression ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Maintaining Myocardial Glucose Utilization in Diabetic Cardiomyopathy Accelerates Mitochondrial Dysfunction

Wende

Schell

et al. 2020

Diabetes

View full text Add to dashboard Cite

Cardiac glucose uptake and oxidation are reduced in diabetes despite hyperglycemia. Mitochondrial dysfunction contributes to heart failure in diabetes. It is unclear whether these changes are adaptive or maladaptive. To directly evaluate the relationship between glucose delivery and mitochondrial dysfunction in diabetic cardiomyopathy, we generated transgenic mice with inducible cardiomyocyte-specific expression of the GLUT4. We examined mice rendered hyperglycemic following lowdose streptozotocin prior to increasing cardiomyocyte glucose uptake by transgene induction. Enhanced myocardial glucose in nondiabetic mice decreased mitochondrial ATP generation and was associated with echocardiographic evidence of diastolic dysfunction. Increasing myocardial glucose delivery after short-term diabetes onset exacerbated mitochondrial oxidative dysfunction. Transcriptomic analysis revealed that the largest changes, driven by glucose and diabetes, were in genes involved in mitochondrial function. This glucosedependent transcriptional repression was in part mediated by O-GlcNAcylation of the transcription factor Sp1. Increased glucose uptake induced direct O-GlcNAcylation of many electron transport chain subunits and other mitochondrial proteins. These findings identify mitochondria as a major target of glucotoxicity. They also suggest that reduced glucose utilization in diabetic cardiomyopathy might defend against glucotoxicity and caution that restoring glucose delivery to the heart in the context of diabetes could accelerate mitochondrial dysfunction by disrupting protective metabolic adaptations.

show abstract

O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities

Cited by 9 publications

References 40 publications

Potential coordination role between O-GlcNAcylation and epigenetics

Potential coordination role between O-GlcNAcylation and epigenetics

Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex

Maintaining Myocardial Glucose Utilization in Diabetic Cardiomyopathy Accelerates Mitochondrial Dysfunction

Contact Info

Product

Resources

About