Titre
The conserved threonine-rich region of the HCF-1<sub>PRO</sub> repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kapuria, V.
Auteure/Auteur
Röhrig, U.F.
Auteure/Auteur
Waridel, P.
Auteure/Auteur
Lammers, F.
Auteure/Auteur
Borodkin, V.S.
Auteure/Auteur
van Aalten, DMF
Auteure/Auteur
Zoete, V.
Auteure/Auteur
Herr, W.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1083-351X
Statut éditorial
Publié
Date de publication
2018-11-16
Volume
293
Numéro
46
Première page
17754
Dernière page/numéro d’article
17768
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities. OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1 <sub>PRO</sub> repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1). Here, we probed the relationship between these distinct glycosylation and proteolytic activities. For proteolysis, the HCF-1 <sub>PRO</sub> repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region. We report that linkage of this HCF-1 <sub>PRO</sub> -repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor R <sub>p</sub> -αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates. Furthermore, it potentiated proteolysis of a non-HCF-1 <sub>PRO</sub> -repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue. Using serine- or glutamate-containing HCF-1 <sub>PRO</sub> -repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together. In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis. These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
Sujets
PID Serval
serval:BIB_2C5B11AB86FD
PMID
Open Access
Oui
Date de création
2018-11-27T08:36:06.135Z
Date de création dans IRIS
2025-05-20T13:58:20Z
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Nom
J. Biol. Chem.-2018-Kapuria-17754-68.pdf
Version du manuscrit
published
Taille
3.34 MB
Format
Adobe PDF
PID Serval
serval:BIB_2C5B11AB86FD.P001
URN
urn:nbn:ch:serval-BIB_2C5B11AB86FD5
Somme de contrôle
(MD5):74c445590b8c00182ffe5aa54297dee5