O-GlcNAc integrates the proteasome and transcriptome to regulate nuclear hormone receptors

Academic Article

Abstract

  • Mechanisms controlling nuclear hormone receptors are a central question to mammalian developmental and disease processes. Herein, we show that a subtle increase in O-GlcNAc levels inhibits activation of nuclear hormone receptors. In vivo, increased levels of O-GlcNAc impair estrogen receptor activation and cause a decrease in mammary ductal side-branching morphogenesis associated with loss of progesterone receptors. Increased O-GlcNAc levels suppress transcriptional expression of coactivators and of the nuclear hormone receptors themselves. Surprisingly, increased O-GlcNAc levels are also associated with increased transcription of genes encoding corepressor proteins NCoR and SMRT. The association of the enzyme O-GlcNAc transferase with these corepressors contributes to specific regulation of nuclear hormone receptors by O-GlcNAc. Overall, transcriptional inhibition is related to the integrated effect of O-GlcNAc by direct modification of critical elements of the transcriptome and indirectly through O-GlcNAc modification of the proteasome. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Bowe DB; Sadlonova A; Toleman CA; Novak Z; Hu Y; Huang P; Mukherjee S; Whitsett T; Frost AR; Paterson AJ
  • Start Page

  • 8539
  • End Page

  • 8550
  • Volume

  • 26
  • Issue

  • 22