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Review
. 2021 Jan;21(1):1.
doi: 10.3892/ol.2020.12262. Epub 2020 Nov 3.

Roles of ten-eleven translocation family proteins and their O-linked β-N-acetylglucosaminylated forms in cancer development

Hong-Jiao Li  1   2 , Yi Wang  3 , Bing-Xin Li  1   2 , Yang Yang  1 , Feng Guan  1 , Xing-Chen Pang  1   2 , Xiang Li  1   2   4
Affiliations
Review

Roles of ten-eleven translocation family proteins and their O-linked β-N-acetylglucosaminylated forms in cancer development

Hong-Jiao Li et al. Oncol Lett. 2021 Jan.

Abstract

Members of the ten-eleven translocation (TET) protein family of which three mammalian TET proteins have been discovered so far, catalyze the sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine which serve an important role in embryonic development and tumor progression. O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is a reversible post-translational modification known to serve important roles in tumorigenesis and metastasis especially in hematopoietic malignancies such as myelodysplastic syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia. O-GlcNAcylation activity requires only two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). OGT catalyzes attachment of GlcNAc sugar to serine, threonine and cytosine residues in proteins, while OGA hydrolyzes O-GlcNAc attached to proteins. Numerous recent studies have demonstrated that TETs can be O-GlcNAcylated by OGT, with consequent alteration of TET activity and stability. The present review focuses on the cellular, biological and biochemical functions of TET and its O-GlcNAcylated form and proposes a model of the role of TET/OGT complex in regulation of target proteins during cancer development. In addition, the present review provides directions for future research in this area.

Keywords: O-GlcNAcylation; TET.

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Figures

Figure 1.
Figure 1.
TET proteins catalyze conversion of 5mC to 5hmC, 5fC and 5caC. Fe, ferrous; ATP, adenosine triphosphate; TETs, ten-eleven translocation family proteins; 5mC, 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine; 5-fc, 5-formylcytosine; 5-caC, 5-carboxylcytosine.
Figure 2.
Figure 2.
Proposed working model of the role of TET/OGT complex in regulation of target proteins during cancer development. TET/OGT complex can work as an epigenetic complex participating in the progress of DNA demethylation. Meanwhile, TET also facilitates the O-GlcNAc modification of histones regulated by OGT. The black arrow represents the product synthesized by the OGT, TET or TET/OGT complex. The blue arrow above represents nuclear import. The blue arrow below represents gene activation. TETs, ten-eleven translocation family proteins; OGT, O-GlcNAc transferase; O-GlcNAcylation, O-linked β-N-acetylglucosaminylation.
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References

    1. Schubeler D. Function and information content of DNA methylation. Nature. 2015;517:321–326. doi: 10.1038/nature14192. - DOI - PubMed
    1. Scott-Browne JP, Lio CJ, Rao A. TET proteins in natural and induced differentiation. Curr Opin Genet Dev. 2017;46:202–208. doi: 10.1016/j.gde.2017.07.011. - DOI - PMC - PubMed
    1. Yang X, Qian K. Protein O-GlcNAcylation: Emerging mechanisms and functions. Nat Rev Mol Cell Biol. 2017;18:452–465. doi: 10.1038/nrm.2017.22. - DOI - PMC - PubMed
    1. Wells L, Vosseller K, Hart GW. Glycosylation of nucleocytoplasmic proteins: Signal transduction and O-GlcNAc. Science. 2001;291:2376–2378. doi: 10.1126/science.1058714. - DOI - PubMed
    1. Hart GW, Housley MP, Slawson C. Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. Nature. 2007;446:1017–1022. doi: 10.1038/nature05815. - DOI - PubMed

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