Adenosine kinase: An epigenetic modulator in development and disease. (July 2021)

• Record Type: Journal Article
• Authors: Murugan, Madhuvika; Fedele, Denise; Millner, David; Alharfoush, Enmar; Vegunta, Geetasravya; Boison, Detlev
• Is Part Of: Neurochemistry international. Volume 147(2021)
• Publication Date: 2021-07
• Subjects: Adenosine kinase -- Epilepsy -- Development -- Epigenetic regulator -- DNA methylation; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2021.105054
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Adenosine kinase (ADK) is the key regulator of adenosine and catalyzes the metabolism of adenosine to 5′-adenosine monophosphate. The enzyme exists in two isoforms: a long isoform (ADK-long, ADK-L) and a short isoform (ADK-short, ADK-S). The two isoforms are developmentally regulated and are differentially expressed in distinct subcellular compartments with ADK-L localized in the nucleus and ADK-S localized in the cytoplasm. The nuclear localization of ADK-L and its biochemical link to the transmethylation pathway suggest a specific role for gene regulation via epigenetic mechanisms. Recent evidence reveals an adenosine receptor-independent role of ADK in determining the global methylation status of DNA and thereby contributing to epigenomic regulation. Here we summarize recent progress in understanding the biochemical interactions between adenosine metabolism by ADK-L and epigenetic modifications linked to transmethylation reactions. This review will provide a comprehensive overview of ADK-associated changes in DNA methylation in developmental, as well as in pathological conditions including brain injury, epilepsy, vascular diseases, cancer, and diabetes. Challenges in investigating the epigenetic role of ADK for therapeutic gains are briefly discussed. Highlights: ADK is developmentally regulated in a cell-type and isoform specific manner. The nuclear ADK-L isoform acts as an epigenetic regulator that drives DNA and histone methylation by clearing adenosine. Epigenetic regulation by ADK is essential for normal neurodevelopment and angiogenesis. ADK mediated epigenetic mechanisms are implicated in several developmental, neurological and pathological conditions.