The emerging insights into catalytic or non-catalytic roles of TET proteins in tumors and neural development.

Hao Lian,Wen-Bin Li,Wei-Lin Jin

doi:10.18632/oncotarget.11412

Hao Lian, Wen-Bin Li + Show 1 more

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https://doi.org/10.18632/oncotarget.11412

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Abstract

The Ten-eleven translocation (TET) proteins have been recently identified as critical regulators in epigenetic modification, especially in the methylation of cytosine in DNA. TET-mediated DNA oxidation plays prominent roles in a wide variety of physiological and pathological processes, especially in tumor and neural development. TET proteins execute stepwise enzymatic conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to the more proverbial enzymatic role of TET proteins, TET proteins also possess non-enzymatic activity, through interacting with some epigenetic modifiers. In this review article, we focus on TET proteins dual activities (catalytic or non-catalytic) in tumor and neural development. Hence, the clarification of TET proteins dual activities will contribute to our further understanding of neural development and may open the possibility of new therapeutic avenues to human tumors.

Highlights

Epigenetic mechanisms, mainly including DNA methylation such as covalent modification of cytosine bases leading to 5-methylcytosine (5mC) and histone modifications, are fundamental to regulate many biological and pathological processes in gene expression, cellular differentiation, embryogenesis, neural development and carcinogenesis
Müller et al reported that nuclear exclusion of TET1 is related to reduction of 5hmC in isocitrate dehydrogenase 1 (IDH1) wild-type gliomas [55]. These findings showed nuclear exclusion of Ten-eleven translocation (TET) proteins may provide a novel mechanism for the reduction in 5hmC from the tumor cells, which is independent from IDH1 status
Kraus et al have reported that 5hmC levels in gliomas are significantly lower compared to normal brain tissue www.impactjournals.com/oncotarget and 5hmC values in glioblastoma multiforme (GBM) are lowest [23].Intriguingly, Cao and his team have demonstrated that TET2 resolves inflammation via recruiting Hdac2 to selectively inhibit IL-6 in innate myeloid cells, which is independent of its enzymatic activity [12]

Summary

Introduction

Epigenetic mechanisms, mainly including DNA methylation such as covalent modification of cytosine bases leading to 5-methylcytosine (5mC) and histone modifications, are fundamental to regulate many biological and pathological processes in gene expression, cellular differentiation, embryogenesis, neural development and carcinogenesis. These studies suggest that TET enzymes catalytic products, especially 5hmC, are likely multifunctional modification that is utilized either in the demethylation pathway or as a stable epigenetic mark itself, depending on the cell type and the genomic location of the modification during neural development (Table 1).

Results

Conclusion