Unknown

Dataset Information

0

Deconstruction of O-glycosylation--GalNAc-T isoforms direct distinct subsets of the O-glycoproteome.


ABSTRACT: 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 a comprehensive 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.

SUBMITTER: Schjoldager KT 

PROVIDER: S-EPMC4693523 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Deconstruction of O-glycosylation--GalNAc-T isoforms direct distinct subsets of the O-glycoproteome.

Schjoldager Katrine T KT   Joshi Hiren J HJ   Kong Yun Y   Goth Christoffer K CK   King Sarah Louise SL   Wandall Hans H HH   Bennett Eric P EP   Vakhrushev Sergey Y SY   Clausen Henrik H  

EMBO reports 20151113 12


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  ...[more]

Similar Datasets

2015-09-30 | E-MTAB-3844 | biostudies-arrayexpress
| PRJEB10772 | ENA
| S-EPMC6295722 | biostudies-literature
| S-EPMC3655468 | biostudies-literature
2019-06-24 | PXD009955 | Pride
| S-EPMC3617340 | biostudies-literature
| S-EPMC4256479 | biostudies-literature
| S-EPMC2859625 | biostudies-literature
| S-EPMC6393581 | biostudies-literature
| S-EPMC9996832 | biostudies-literature