zDHHC20-driven S-palmitoylation of CD80 is required for its costimulatory function.
Acta Pharmacol Sin
; 45(6): 1214-1223, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38467718
ABSTRACT
CD80 is a transmembrane glycoprotein belonging to the B7 family, which has emerged as a crucial molecule in T cell modulation via the CD28 or CTLA4 axes. CD80-involved regulation of immune balance is a finely tuned process and it is important to elucidate the underlying mechanism for regulating CD80 function. In this study we investigated the post-translational modification of CD80 and its biological relevance. By using a metabolic labeling strategy, we found that CD80 was S-palmitoylated on multiple cysteine residues (Cys261/262/266/271) in both the transmembrane and the cytoplasmic regions. We further identified zDHHC20 as a bona fide palmitoyl-transferase determining the S-palmitoylation level of CD80. We demonstrated that S-palmitoylation protected CD80 protein from ubiquitination degradation, regulating the protein stability, and ensured its accurate plasma membrane localization. The palmitoylation-deficient mutant (4CS) CD80 disrupted these functions, ultimately resulting in the loss of its costimulatory function upon T cell activation. Taken together, our results describe a new post-translational modification of CD80 by S-palmitoylation as a novel mechanism for the regulation of CD80 upon T cell activation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aciltransferasas
/
Activación de Linfocitos
/
Antígeno B7-1
/
Lipoilación
Límite:
Humans
Idioma:
En
Revista:
Acta Pharmacol Sin
Asunto de la revista:
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China