Revisiting the human polypeptide GalNAc-T1 and T13 paralogs.

Abstract:

:Polypeptide GalNAc-transferases (GalNAc-Ts) constitute a family of 20 human glycosyltransferases (comprising 9 subfamilies), which initiate mucin-type O-glycosylation. The O-glycoproteome is thought to be differentially regulated via the different substrate specificities and expression patterns of each GalNAc-T isoforms. Here, we present a comprehensive in vitro analysis of the peptide substrate specificity of GalNAc-T13, showing that it essentially overlaps with the ubiquitous expressed GalNAc-T1 isoform found in the same subfamily as T13. We have also identified and partially characterized nine splice variants of GalNAc-T13, which add further complexity to the GalNAc-T family. Two variants with changes in their lectin domains were characterized by in vitro glycosylation assays, and one (Δ39Ex9) was inactive while the second one (Ex10b) had essentially unaltered activity. We used reverse transcription-polymerase chain reaction analysis of human neuroblastoma cell lines, normal brain and a small panel of neuroblastoma tumors to demonstrate that several splice variants (Ex10b, ΔEx9, ΔEx2-7 and ΔEx6/8-39bpEx9) were highly expressed in tumor cell lines compared with normal brain, although the functional implications remain to be unveiled. In summary, the GalNAc-T13 isoform is predicted to function similarly to GalNAc-T1 against peptide substrates in vivo, in contrast to a prior report, but is unique by being selectively expressed in the brain.

journal_name

Glycobiology

journal_title

Glycobiology

authors

Festari MF,Trajtenberg F,Berois N,Pantano S,Revoredo L,Kong Y,Solari-Saquieres P,Narimatsu Y,Freire T,Bay S,Robello C,Bénard J,Gerken TA,Clausen H,Osinaga E

doi

10.1093/glycob/cww111

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

140-153

issue

2

eissn

0959-6658

issn

1460-2423

pii

cww111

journal_volume

27

pub_type

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