Epigenetic dysregulation in cancers by isocitrate dehydrogenase 2 (IDH2).
Adv Protein Chem Struct Biol
; 141: 223-253, 2024.
Article
en En
| MEDLINE
| ID: mdl-38960475
ABSTRACT
Recent advances in genome-wide studies have revealed numerous epigenetic regulations brought about by genes involved in cellular metabolism. Isocitrate dehydrogenase (IDH), an essential enzyme, that converts isocitrate into -ketoglutarate (KG) predominantly in the tricarboxylic acid (TCA) cycle, has gained particular importance due to its cardinal role in the metabolic pathway in cells. IDH1, IDH2, and IDH3 are the three isomeric IDH enzymes that have been shown to regulate cellular metabolism. Of particular importance, IDH2 genes are associated with several cancers, including gliomas, oligodendroglioma, and astrocytomas. These mutations lead to the production of oncometabolite D-2-hydroxyglutarate (D-2-HG), which accumulates in cells promoting tumor growth. The enhanced levels of D-2-HG competitively inhibit α-KG dependent enzymes, inhibiting cell TCA cycle, upregulating the cell growth and survival relevant HIF-1α pathway, promoting DNA hypermethylation related epigenetic activity, all of which synergistically contribute to carcinogenesis. The present review discusses epigenetic mechanisms inIDH2 regulation in cells and further its clinical implications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Epigénesis Genética
/
Isocitrato Deshidrogenasa
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Adv Protein Chem Struct Biol
Asunto de la revista:
BIOLOGIA
/
BIOQUIMICA
Año:
2024
Tipo del documento:
Article