@article{APS11037,
author = {Bin Lu and Yi-yun Sun and Bo-ya Chen and Bo Yang and Qiao-jun He and Jun Li and Ji Cao},
title = {zDHHC20-driven S-palmitoylation of CD80 is required for its costimulatory function},
journal = {Acta Pharmacologica Sinica},
volume = {45},
number = {6},
year = {2024},
keywords = {},
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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11037}
}