The potential role of O-GlcNAc modification in cancer epigenetics

Forma, Ewa; Jóźwiak, Paweł; Bryś, Magdalena; Krześlak, Anna

doi:10.2478/s11658-014-0204-6

Cited by 24 publications

(14 citation statements)

References 119 publications

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“…Aberrant expression and activities of O-GlcNAc cycling enzymes, especially OGT, have been reported in all human cancers studied to date (267). Altered cellular metabolism is a major hallmark of cancer.…”

Section: O-glcnac and Cancermentioning

confidence: 99%

Nutrient regulation of signaling and transcription

Hart

2019

Journal of Biological Chemistry

279

225

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O‐GlcNAc cycles on and off thousands of nucleocytoplasmic proteins and has extensive crosstalk with protein phosphorylation. O‐GlcNAc cycles on nearly all proteins involved in transcription, where it regulates gene expression in response to nutrients. O‐GlcNAc also regulates the cycling of the TATA‐binding (TBP) protein on and off DNA during the transcription cycle. Targeted, inducible, deletion of the O‐GlcNAc Transferase (OGT) in aCAMKII positive (excitatory) neurons of adult mice results in a morbidly obese mouse with a satiety defect. Thus, O‐GlcNAcylation not only serves as a nutrient sensor in all cells, but also is directly involved in appetite regulation. O‐GlcNAcylation also plays an important role in the trafficking of the AMPA receptors in neurons and in the development of functional synaptic spines. Recent studies have shown that more than one‐half of all human protein kinases are modified by O‐GlcNAc and all kinases that have been tested are indeed regulated in some way by the sugar. Abnormal O‐GlcNAcylation of CAMKII contributes directly to diabetic cardiomyopathy and to arrhythmias associated with diabetes. Prolonged elevation of O‐GlcNAc, as occurs in diabetes, contributes directly to diabetic complications and is a major mechanism of glucose toxicity. Drugs that elevate O‐GlcNAcylation in the brain, which, in‐turn, prevents hyperphosphorylation, appear to be of benefit for the treatment of Alzheimer's disease in animal models. To date, all cancers have elevated O‐GlcNAc cycling, which may play a key role in the regulation of metabolism in cancer cells. Support or Funding Information Supported by NIH P01HL107153, R01GM116891, R01DK61671, and N01‐HV‐00240. Dr. Hart receives a share of royalty received by the university on sales of the CTD 110.6 antibody, which are managed by JHU. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Section: O-glcnac and Cancermentioning

confidence: 99%

Nutrient regulation of signaling and transcription

Hart

2019

Journal of Biological Chemistry

279

225

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“…14,15 The physiological importance of O-GlcNAcylation is further emphasized by the fact that defects in its regulation have been associated with human pathologies, such as diabetes, neurodegenerative diseases, and cancer. [16][17][18][19][20] O-GlcNAcylation signaling was proposed to play important roles in regulating the epigenome. 1 complexes, stability, and activity.…”

Section: Undetectable Histone O-glcnacylation In Mammalian Cellsmentioning

confidence: 99%

Undetectable histone O-GlcNAcylation in mammalian cells

et al. 2015

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O-GlcNAcylation is a posttranslational modification catalyzed by the O-Linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and reversed by O-GlcNAcase (OGA). Numerous transcriptional regulators, including chromatin modifying enzymes, transcription factors, and co-factors, are targeted by O-GlcNAcylation, indicating that this modification is central for chromatin-associated processes. Recently, OGT-mediated O-GlcNAcylation was reported to be a novel histone modification, suggesting a potential role in directly coordinating chromatin structure and function. In contrast, using multiple biochemical approaches, we report here that histone O-GlcNAcylation is undetectable in mammalian cells. Conversely, O-GlcNAcylation of the transcription regulators Host Cell Factor-1 (HCF-1) and Ten-Eleven Translocation protein 2 (TET2) could be readily observed. Our study raises questions on the occurrence and abundance of O-GlcNAcylation as a histone modification in mammalian cells and reveals technical complications regarding the detection of genuine protein O-GlcNAcylation. Therefore, the identification of the specific contexts in which histone O-GlcNAcylation might occur is still to be established.

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“…Loss of BAP1 results in a modest accumulation of HCF1, which promotes transition from G1 to S phase 6. BAP1 also deubiquitinates O-linked N-acetylglucosamine transferase (OGT), which in turn modifies and activates HCF1 7. BAP1 has been shown to form a ternary complex with HCF1 and transcription factor Ying Yang 1 (YY1), which controls cellular proliferation 8.…”

Section: Structure and Functionmentioning

confidence: 99%

Gene of the month:BAP1

et al. 2016

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The BAP1 gene (BRCA1-associated protein 1) is a tumour suppressor gene that encodes a deubiquitinating enzyme (DUB), regulating key cellular pathways, including cell cycle, cellular differentiation, transcription and DNA damage response. Germline BAP1 mutations cause a novel cancer syndrome characterised by early onset of multiple atypical Spitz tumours and increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma and various other malignancies. Recognising the clinicopathological features of specific BAP1-deficient tumours is crucial for early screening/tumour detection, with significant impact on patient outcome.

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The potential role of O-GlcNAc modification in cancer epigenetics

Cited by 24 publications

References 119 publications

Nutrient regulation of signaling and transcription

Nutrient regulation of signaling and transcription

Undetectable histone O-GlcNAcylation in mammalian cells

Gene of the month:BAP1

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