O-GlcNAcylation regulates the stability and enzymatic activity of the histone methyltransferase EZH2
Abstract
Glycosylation is considered to be a major posttranslational modification, and O-GlcNAcylation is known to affect protein folding and function. In this study, we show that the methyltransferase EZH2, which catalyzes the methylation of histone 3 at lysine 27 to form H3K27m3, requires O-GlcNAcylation to enhance its stability and enzymatic activity to promote tumor progression. We further show that the O-GlcNAcylation in the N-terminal region of EZH2 stabilizes the enzyme and the O-GlcNAcylation at S729 in the catalytic domain is essential for its activity of di- and trimethylation. This study indicates that selective inhibition of EZH2 O-GlcNAcylation may suppress the methylation of H3K27 and thus inhibit tumor progression.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- July 2018
- DOI:
- 10.1073/pnas.1801850115
- Bibcode:
- 2018PNAS..115.7302L