Global mapping of GalNAc-T isoform-specificities and O-glycosylation site-occupancy in a tissue-forming human cell line
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Global mapping of GalNAc-T isoform-specificities and O-glycosylation site-occupancy in a tissue-forming human cell line. / Nielsen, Mathias I.; de Haan, Noortje; Kightlinger, Weston; Ye, Zilu; Dabelsteen, Sally; Li, Minyan; Jewett, Michael C.; Bagdonaite, Ieva; Vakhrushev, Sergey Y.; Wandall, Hans H.
In: Nature Communications, Vol. 13, 6257, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Global mapping of GalNAc-T isoform-specificities and O-glycosylation site-occupancy in a tissue-forming human cell line
AU - Nielsen, Mathias I.
AU - de Haan, Noortje
AU - Kightlinger, Weston
AU - Ye, Zilu
AU - Dabelsteen, Sally
AU - Li, Minyan
AU - Jewett, Michael C.
AU - Bagdonaite, Ieva
AU - Vakhrushev, Sergey Y.
AU - Wandall, Hans H.
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - Mucin-type-O-glycosylation on proteins is integrally involved in human health and disease and is coordinated by an enzyme family of 20 N-acetylgalactosaminyltransferases (GalNAc-Ts). Detailed knowledge on the biological effects of site-specific O-glycosylation is limited due to lack of information on specific glycosylation enzyme activities and O-glycosylation site-occupancies. Here we present a systematic analysis of the isoform-specific targets of all GalNAc-Ts expressed within a tissue-forming human skin cell line, and demonstrate biologically significant effects of O-glycan initiation on epithelial formation. We find over 300 unique glycosylation sites across a diverse set of proteins specifically regulated by one of the GalNAc-T isoforms, consistent with their impact on the tissue phenotypes. Notably, we discover a high variability in the O-glycosylation site-occupancy of 70 glycosylated regions of secreted proteins. These findings revisit the relevance of individual O-glycosylation sites in the proteome, and provide an approach to establish which sites drive biological functions.
AB - Mucin-type-O-glycosylation on proteins is integrally involved in human health and disease and is coordinated by an enzyme family of 20 N-acetylgalactosaminyltransferases (GalNAc-Ts). Detailed knowledge on the biological effects of site-specific O-glycosylation is limited due to lack of information on specific glycosylation enzyme activities and O-glycosylation site-occupancies. Here we present a systematic analysis of the isoform-specific targets of all GalNAc-Ts expressed within a tissue-forming human skin cell line, and demonstrate biologically significant effects of O-glycan initiation on epithelial formation. We find over 300 unique glycosylation sites across a diverse set of proteins specifically regulated by one of the GalNAc-T isoforms, consistent with their impact on the tissue phenotypes. Notably, we discover a high variability in the O-glycosylation site-occupancy of 70 glycosylated regions of secreted proteins. These findings revisit the relevance of individual O-glycosylation sites in the proteome, and provide an approach to establish which sites drive biological functions.
U2 - 10.1038/s41467-022-33806-8
DO - 10.1038/s41467-022-33806-8
M3 - Journal article
C2 - 36270990
AN - SCOPUS:85140215967
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 6257
ER -
ID: 324363594