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HCF-1 is cleaved in the active site of O-GlcNAc transferase.

ABSTRACT: Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.

SUBMITTER: Lazarus MB

PROVIDER: S-EPMC3930058 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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HCF-1 is cleaved in the active site of O-GlcNAc transferase.

Lazarus Michael B MB Jiang Jiaoyang J Kapuria Vaibhav V Bhuiyan Tanja T Janetzko John J Zandberg Wesley F WF Vocadlo David J DJ Herr Winship W Walker Suzanne S

Science (New York, N.Y.) 20131201 6163

Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site ab ...[more]

PMID: 24311690

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