A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity

PLoS Pathogens

Mark Helm¹  Ricarda Gaentzsch¹  Ayala Tovy²  Rama Siman Tov²  Serge Ankri³ 

[1] Department of Chemistry, The Pharmacy and Molecular Biotechnology Institute, Ruprecht-Karls University of Heidelberg, Heidelberg, Germany;Department of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel;The Pharmacy and Biochemistry Institute, Johannes Gutenberg University, Mainz, Germany

关键词: Trophozoites;    DNA methylation;    Transfer RNA;    Glucose;    Immunoprecipitation;    Polymerase chain reaction;    Methylation;    Methyltransferases;   

DOI  :  10.1371/journal.ppat.1000775

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Cytosine-5 methyltransferases of the Dnmt2 family function as DNA and tRNA methyltransferases. Insight into the role and biological significance of Dnmt2 is greatly hampered by a lack of knowledge about its protein interactions. In this report, we address the subject of protein interaction by identifying enolase through a yeast two-hybrid screen as a Dnmt2-binding protein. Enolase, which is known to catalyze the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), was shown to have both a cytoplasmatic and a nuclear localization in the parasite Entamoeba histolytica. We discovered that enolase acts as a Dnmt2 inhibitor. This unexpected inhibitory activity was antagonized by 2-PG, which suggests that glucose metabolism controls the non-glycolytic function of enolase. Interestingly, glucose starvation drives enolase to accumulate within the nucleus, which in turn leads to the formation of additional enolase-E.histolytica DNMT2 homolog (Ehmeth) complex, and to a significant reduction of the tRNAAsp methylation in the parasite. The crucial role of enolase as a Dnmt2 inhibitor was also demonstrated in E.histolytica expressing a nuclear localization signal (NLS)-fused-enolase. These results establish enolase as the first Dnmt2 interacting protein, and highlight an unexpected role of a glycolytic enzyme in the modulation of Dnmt2 activity.

【 授权许可】

CC BY