Artemisinin inhibits NRas palmitoylation by targeting the protein acyltransferase ZDHHC6.
Cell Chem Biol
; 29(3): 530-537.e7, 2022 03 17.
Article
en En
| MEDLINE
| ID: mdl-34358442
ABSTRACT
Protein S-palmitoylation is a post-translational modification that plays a crucial role in cancer cells by regulating the function and localization of oncoproteins and tumor suppressor proteins. Here, we identify artemisinin (ART), a clinically approved antimalarial endoperoxide natural product with promising anticancer activities, as an inhibitor of the ER-residing palmitoyl transferase ZDHHC6 in cancer cells using a chemoproteomic approach. We show that ART covalently binds and inhibits ZDHHC6 to reduce palmitoylation of the oncogenic protein NRas, disrupt NRas subcellular localization, and attenuate the downstream pro-proliferative signaling cascades. Our study identifies artemisinin as a non-lipid-based palmitoylation inhibitor targeting a specific palmitoyl acyltransferase and provides valuable mechanistic insights into the anticancer activity of artemisinins that are currently being studied in human clinical trials for different cancers.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artemisininas
/
Lipoilación
Límite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos