Distinct OGT-Binding Sites Promote HCF-1 Cleavage.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_867855A8F516
Type
Article: article from journal or magazin.
Collection
Publications
Title
Distinct OGT-Binding Sites Promote HCF-1 Cleavage.
Journal
Plos One
Author(s)
Bhuiyan T., Waridel P., Kapuria V., Zoete V., Herr W.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
10
Number
8
Pages
e0136636
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Human HCF-1 (also referred to as HCFC-1) is a transcriptional co-regulator that undergoes a complex maturation process involving extensive O-GlcNAcylation and site-specific proteolysis. HCF-1 proteolysis results in two active, noncovalently associated HCF-1N and HCF-1C subunits that regulate distinct phases of the cell-division cycle. HCF-1 O-GlcNAcylation and site-specific proteolysis are both catalyzed by O-GlcNAc transferase (OGT), which thus displays an unusual dual enzymatic activity. OGT cleaves HCF-1 at six highly conserved 26 amino acid repeat sequences called HCF-1PRO repeats. Here we characterize the substrate requirements for OGT cleavage of HCF-1. We show that the HCF-1PRO-repeat cleavage signal possesses particular OGT-binding properties. The glutamate residue at the cleavage site that is intimately involved in the cleavage reaction specifically inhibits association with OGT and its bound cofactor UDP-GlcNAc. Further, we identify a novel OGT-binding sequence nearby the first HCF-1PRO-repeat cleavage signal that enhances cleavage. These results demonstrate that distinct OGT-binding sites in HCF-1 promote proteolysis, and provide novel insights into the mechanism of this unusual protease activity.
Keywords
Binding Sites, Cytokinesis/genetics, Glutamic Acid/metabolism, HeLa Cells, Host Cell Factor C1/genetics, Host Cell Factor C1/metabolism, Humans, N-Acetylglucosaminyltransferases/genetics, N-Acetylglucosaminyltransferases/metabolism, Protein Subunits/genetics, Protein Subunits/metabolism, Proteolysis, Repetitive Sequences, Amino Acid/genetics, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
03/09/2015 15:32
Last modification date
20/08/2019 15:45
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