Proteomics

Dataset Information

0

Probing the contribution of individual polypeptide GalNAc-transferase isoforms to the O-glycoproteome by inducible expression in isogenic cell lines


ABSTRACT: The GalNAc-type O-glycoproteome is orchestrated by a large family of polypeptide GalNAc-transferase isoenzymes (GalNAc-Ts) with partially overlapping contributions to the O-glycoproteome as well as distinct non-redundant functions. Increasing evidence indicate that individual GalNAc-Ts co-regulate and fine-tune specific protein functions in health and disease, and deficiencies in individual GALNT genes underlie congenital diseases with distinct phenotypes. Studies of GalNAc-T specificities have mainly been performed with in vitro enzyme assays using short peptide substrate, but recently quantitative differential O-glycoproteomics of isogenic cells with and without GALNT genes has enabled a more unbiased exploration of the non-redundant contributions of individual GalNAc-Ts. Both approaches suggest that fairly small subsets of O-glycosites are non-redundantly regulated by specific GalNAc-Ts, but how these isoenzymes orchestrate regulation amongst competing redundant substrates is unclear. To explore this, we developed isogenic cell model systems with Tet-On inducible expression of two GalNAc-T genes, GALNT2 and GALNT11, in a knockout background. Using quantitative O-glycoproteomics with TMT labelling we found that isoform-specific glycosites were glycosylated in a dose dependent manner, and induction of GalNAc-T2 or T11 produced discrete glycosylation effects without affecting the major part of the glycoproteome. The results support the findings that individual GalNAc-T isoenzymes can serve in fine-tuned regulation of distinct protein functions

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Sergey Vakhrushev  

LAB HEAD: Sergey Vakhrushev

PROVIDER: PXD010155 | Pride | 2018-10-16

REPOSITORIES: Pride

altmetric image

Publications

Probing the contribution of individual polypeptide GalNAc-transferase isoforms to the <i>O</i>-glycoproteome by inducible expression in isogenic cell lines.

Hintze John J   Ye Zilu Z   Narimatsu Yoshiki Y   Madsen Thomas Daugbjerg TD   Joshi Hiren J HJ   Goth Christoffer K CK   Linstedt Adam A   Bachert Collin C   Mandel Ulla U   Bennett Eric P EP   Vakhrushev Sergey Y SY   Schjoldager Katrine T KT  

The Journal of biological chemistry 20181016 49


The GalNAc-type <i>O</i>-glycoproteome is orchestrated by a large family of polypeptide GalNAc-transferase isoenzymes (GalNAc-Ts) with partially overlapping contributions to the <i>O</i>-glycoproteome besides distinct nonredundant functions. Increasing evidence indicates that individual GalNAc-Ts co-regulate and fine-tune specific protein functions in health and disease, and deficiencies in individual <i>GALNT</i> genes underlie congenital diseases with distinct phenotypes. Studies of GalNAc-T s  ...[more]

Similar Datasets

2024-04-29 | PXD036213 | Pride
2019-06-24 | PXD009955 | Pride
2015-08-21 | PXD002770 | Pride
2022-10-22 | PXD036791 | Pride
2015-09-30 | E-MTAB-3844 | biostudies-arrayexpress
2024-05-23 | PXD047845 | Pride
2020-04-22 | PXD018048 | Pride
2019-04-01 | PXD011045 | Pride
2020-05-22 | PXD016618 | Pride
2020-10-19 | PXD017510 | Pride