O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic.

Details

Serval ID
serval:BIB_3561881A8678
Type
Article: article from journal or magazin.
Collection
Publications
Title
O-GlcNAcylation prevents aggregation of the Polycomb group repressor polyhomeotic.
Journal
Developmental cell
Author(s)
Gambetta M.C., Müller J.
ISSN
1878-1551 (Electronic)
ISSN-L
1534-5807
Publication state
Published
Issued date
08/12/2014
Peer-reviewed
Oui
Volume
31
Number
5
Pages
629-639
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure to repress Polycomb target genes. The Polycomb protein Polyhomeotic (Ph), an Ogt substrate, forms large aggregates in the absence of O-GlcNAcylation both in vivo and in vitro. O-GlcNAcylation of a serine/threonine (S/T) stretch in Ph is critical to prevent nonproductive aggregation of both Drosophila and human Ph via their C-terminal sterile alpha motif (SAM) domains in vitro. Full Ph repressor activity in vivo requires both the SAM domain and O-GlcNAcylation of the S/T stretch. We demonstrate that Ph mutants lacking the S/T stretch reproduce the phenotype of ogt mutants, suggesting that the S/T stretch in Ph is the key Ogt substrate in Drosophila. We propose that O-GlcNAcylation is needed for Ph to form functional, ordered assemblies via its SAM domain.
Keywords
Acetylglucosamine/metabolism, Animals, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster/embryology, Drosophila melanogaster/metabolism, Gene Expression Regulation, Developmental/physiology, Gene Knockout Techniques/methods, Humans, N-Acetylglucosaminyltransferases/metabolism, Polycomb Repressive Complex 1/genetics, Polycomb Repressive Complex 1/metabolism, Repressor Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
19/07/2018 11:02
Last modification date
21/08/2019 6:35
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