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

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  • Author(s): Gambetta MC;Gambetta MC; Müller J; Müller J
  • Source:
    Developmental cell [Dev Cell] 2014 Dec 08; Vol. 31 (5), pp. 629-39. Date of Electronic Publication: 2014 Nov 26.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101120028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1551 (Electronic) Linking ISSN: 15345807 NLM ISO Abbreviation: Dev Cell Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge, Mass. : Cell Press, c2001-
    • Subject Terms:
      Acetylglucosamine/*metabolism ; DNA-Binding Proteins/*metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*metabolism ; Polycomb Repressive Complex 1/*metabolism ; Repressor Proteins/*metabolism; Animals ; DNA-Binding Proteins/genetics ; Drosophila Proteins/genetics ; Drosophila melanogaster/embryology ; Gene Expression Regulation, Developmental/physiology ; Gene Knockout Techniques/methods ; Humans ; N-Acetylglucosaminyltransferases/metabolism ; Polycomb Repressive Complex 1/genetics
    • 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.
      (Copyright © 2014 Elsevier Inc. All rights reserved.)
    • Comments:
      Comment in: Dev Cell. 2014 Dec 8;31(5):521-2. (PMID: 25490262)
    • Accession Number:
      0 (DNA-Binding Proteins)
      0 (Drosophila Proteins)
      0 (Repressor Proteins)
      0 (ph-d protein, Drosophila)
      EC 2.3.2.27 (Polycomb Repressive Complex 1)
      EC 2.4.1.- (N-Acetylglucosaminyltransferases)
      EC 2.4.1.- (O-GlcNAc transferase)
      V956696549 (Acetylglucosamine)
    • Publication Date:
      Date Created: 20141204 Date Completed: 20150225 Latest Revision: 20191210
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.devcel.2014.10.020
    • Accession Number:
      25468754