zDHHC20-driven S-palmitoylation of CD80 is required for its costimulatory function  

作　　者：Bin Lu Yi-yun Sun Bo-ya Chen Bo Yang Qiao-jun He Jun Li Ji Cao 

机构地区：[1]Institute of Pharmacology and Toxicology,Zhejiang Province Key Laboratory of Anti-Cancer Drug Research,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou,310000,China [2]Engineering Research Center of Innovative Anticancer Drugs,Ministry of Education,Hangzhou,310000,China [3]Center for Medical Research and Innovation in Digestive System Tumors,Ministry of Education,Hangzhou,310000,China [4]The Innovation Institute for Artificial Intelligence in Medicine,Zhejiang University,Hangzhou,310000,China [5]School of Medicine,Hangzhou City University,Hangzhou,310000,China [6]Cancer Center of Zhejiang University,Hangzhou,310000,China [7]Department of Colorectal Surgery and Oncology(Key Laboratory of Cancer Prevention and Intervention,China National Ministry of Education,Key Laboratory of Molecular Biology in Medical Sciences,Zhejiang Province,China),The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310000,China [8]Zhejiang Provincial Clinical Research Center for CANCER,Hangzhou,310000,China

出　　处：《Acta Pharmacologica Sinica》2024年第6期1214-1223,共10页中国药理学报（英文版）

基　　金：supported by grants from Zhejiang Provincial Natural Science Foundation of China(LR22H310002 to JC);the National Natural Science Foundation of China(No.82330114 to QH);the Fundamental Research Funds for the Central Universities(226-2023-00059).

摘　　要：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.

关 键 词：CD80 zDHHC20 S-palmitoylation costimulatory signals T cell activation 

分 类 号：R96[医药卫生—药理学]