期刊
EMBO REPORTS
卷 16, 期 12, 页码 1713-1722出版社
WILEY
DOI: 10.15252/embr.201540796
关键词
apolipoproteins; dimethylation; GALNT; mass spectrometry
资金
- Danish Research Councils (Sapere Aude Research Talent Grant)
- Mizutani Foundation
- Kirsten og Freddy Johansen Fonden
- A.P. Moller og Hustru Chastine Mc-Kinney Mollers Fond til Almene Formaal
- Novo Nordisk Foundation
- program of excellence from the University of Copenhagen [CDO2016]
- Danish National Research Foundation [DNRF107]
GalNAc-type O-glycosylation is found on most proteins trafficking through the secretory pathway in metazoan cells. The O-glycoproteome is regulated by up to 20 polypeptide GalNAc-Ts and the contributions and biological functions of individual GalNAc-Ts are poorly understood. Here, we used a zinc-finger nuclease (ZFN)-directed knockout strategy to probe the contributions of the major GalNAc-Ts (GalNAc-T1 and GalNAc-T2) in liver cells and explore how the GalNAc-T repertoire quantitatively affects the O-glycoproteome. We demonstrate that the majority of the O-glycoproteome is covered by redundancy, whereas distinct subsets of substrates are modified by non-redundant functions of GalNAc-T1 and GalNAc-T2. The non-redundant O-glycoproteome subsets and specific transcriptional responses for each isoform are related to different cellular processes; for the GalNAc-T2 isoform, these support a role in lipid metabolism. The results demonstrate that GalNAc-Ts have different non-redundant glycosylation functions, which may affect distinct cellular processes. The data serves as acomprehensive resource for unique GalNAc-T substrates. Our study provides a new view of the differential regulation of the O-glycoproteome, suggesting that the plurality of GalNAc-Ts arose to regulate distinct protein functions and cellular processes.
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