Oxygen regulation of TET enzymes.

Authors
Matuleviciute, Rugile 
Cunha, Pedro P 
Foskolou, Iosifina P 

Change log
Abstract

Hypoxia has a significant impact on many physiological and pathological processes. Over the recent years, its role in modulation of epigenetic remodelling has also become clearer. In cancer, low oxygen environments and aberrant epigenomes often go hand in hand, and changes in DNA methylation are now commonly recognised as potential outcome indicators. TET (ten-eleven translocation) family enzymes are alpha-ketoglutarate-, iron- and oxygen-dependent DNA demethylases and are key players in these processes. Although TETs have historically been considered tumour suppressors, recent studies suggest that their functions in cancer might not be straightforward. Recently, inhibition of TETs has been reported to have positive impact in cancer immunotherapy and vaccination studies. This underlines the current interest in developing targeted pharmaceutical inhibitors of these enzymes. Here, we will survey the complexity of TET roles in cancer, and its hypoxic modulation, as well as highlight the potential of these enzymes as therapeutic targets.

Publication Date
2021-12
Online Publication Date
2021-01-29
Acceptance Date
2021-01-04
Keywords
5hmC, TET, cancer, hypoxia, immunotherapy, α-KG-dependent enzymes, Animals, Humans, Mixed Function Oxygenases, Neoplasms, Oxygen
Journal Title
FEBS J
Journal ISSN
1742-464X
1742-4658
Volume Title
288
Publisher
Wiley
Sponsorship
Wellcome Trust (214283/Z/18/Z)