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The potential role of O-GlcNAc modification in cancer epigenetics

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.

Abbreviations

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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Forma, E., Jóźwiak, P., Bryś, M. et al. The potential role of O-GlcNAc modification in cancer epigenetics. Cell Mol Biol Lett 19, 438–460 (2014). https://doi.org/10.2478/s11658-014-0204-6

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Keywords

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