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. 2014 Aug 20;19(3):438–460. doi: 10.2478/s11658-014-0204-6

The potential role of O-GlcNAc modification in cancer epigenetics

Ewa Forma 1, Paweł Jóźwiak 1, Magdalena Bryś 1, Anna Krześlak 1,✉
PMCID: PMC6275943  PMID: 25141978

Abstract

There is no doubt that cancer is not only a genetic disease but that it can also occur due to epigenetic abnormalities. Diet and environmental factors can alter the scope of epigenetic regulation. The results of recent studies suggest that O-GlcNAcylation, which involves the addition of N-acetylglucosamine on the serine or threonine residues of proteins, may play a key role in the regulation of the epigenome in response to the metabolic status of the cell. Two enzymes are responsible for cyclic O-GlcNAcylation: O-GlcNAc transferase (OGT), which catalyzes the addition of the GlcNAc moiety to target proteins; and O-GlcNAcase (OGA), which removes the sugar moiety from proteins. Aberrant expression of O-GlcNAc cycling enzymes, especially OGT, has been found in all studied human cancers. OGT can link the cellular metabolic state and the epigenetic status of cancer cells by interacting with and modifying many epigenetic factors, such as HCF-1, TET, mSin3A, HDAC, and BAP1. A growing body of evidence from animal model systems also suggests an important role for OGT in polycomb-dependent repression of genes activity. Moreover, O-GlcNAcylation may be a part of the histone code: O-GlcNAc residues are found on all core histones.

Keywords: O-GlcNAcylation, Cancer, O-GlcNAc transferase, Histone modifications, Host cell factor 1, Ten-eleven translocation, Polycomb

Full Text

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Abbreviations used

5-hmC

5-hydoxymethylcytosine

BAP1

BRCA1-associated protein 1

BMI-1

B lymphoma Mo-MLV insertion region 1 homolog

BMP

bone morphogenic protein

EMT

epithelial-mesenchymal transition

FGF

fibroblast growth factor

GFAT

glutamine:fructose-6-phosphate amidotransferase

H3K4me3

trimethylation of histone H3 at lysine 4

HBP

hexosamine biosynthetic pathway

HCF-1

host cell factor 1

HPC

human polycomb

HPH

human polyhomeotic

MLL

myeloid/lymphoid or mixed-lineage leukemia

OGA

β-N-acetylglucosaminidase

OGT

O-linked N-acetylglucosamine transferase

PcG

polycomb group protein

pRb

the product of the retinoblastoma gene

PRC

polycomb repression complex

RING 1A

really interesting new gene 1A

TET

ten eleven translocation

THAP

Thanatosassociated protein

TPA

12-O-tetradecanoylphorbol 13-acetate

ubH2B

ubiquitylated histone H2B

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