Functional implications of fumarate-induced cysteine succination.
Trends Biochem Sci
; 49(9): 775-790, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38876954
ABSTRACT
Mutations in metabolic enzymes are associated with hereditary and sporadic forms of cancer. For example, loss-of-function mutations affecting fumarate hydratase (FH), the tricarboxylic acid (TCA) cycle enzyme, result in the accumulation of millimolar levels of fumarate that cause an aggressive form of kidney cancer. A distinct feature of fumarate is its ability to spontaneously react with thiol groups of cysteines in a chemical reaction termed succination. Although succination of a few proteins has been causally implicated in the molecular features of FH-deficient cancers, the stoichiometry, wider functional consequences, and contribution of succination to disease development remain largely unexplored. We discuss the functional implications of fumarate-induced succination in FH-deficient cells, the available methodologies, and the current challenges in studying this post-translational modification.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cisteína
/
Fumarato Hidratasa
/
Fumaratos
Límite:
Animals
/
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article