Regulation of keratinocyte differentiation by O-GlcNAcylation

J Dermatol Sci. 2014 Jul;75(1):10-5. doi: 10.1016/j.jdermsci.2014.04.010. Epub 2014 Apr 30.

Abstract

Background: O-linked β-N-acetylglucosamine (O-GlcNAc) modification is one of the posttranslational modification, emerging as an important regulatory mechanism in various cellular events.

Objective: We attempted to investigate whether O-GlcNAcylation is involved in keratinocyte differentiation.

Methods: Immunohistochemistry and Western blot were performed to demonstrate O-GlcNAcylation in keratinocyte differentiation.

Results: During calcium-induced keratinocyte differentiation, overall O-GlcNAcylation was decreased in a temporal manner. We focused our attention on transcription factor Sp-1, which is implicated in keratinocyte differentiation. Total Sp-1 level did not change during keratinocyte differentiation. However, O-GlcNAcylated Sp-1 was decreased in a keratinocyte differentiation-dependent manner. Interestingly, transcriptional activity of Sp-1, in terms of involucrin and loricrin promoter activities, was markedly increased by overexpression of O-GlcNAcase (OGA). In addition, membrane permeable non-O-GlcNAcylated Sp-1 did show transcriptional activity, while membrane permeable O-GlcNAcylated Sp-1 did not, suggesting O-GlcNAcylated Sp-1 is an inactive form in keratinocyte differentiation.

Conclusion: Our results reveal that O-GlcNAcylation is a dynamic regulatory mechanism for keratinocyte differentiation.

Keywords: Keratinocyte differentiation; O-GlcNAcylation; Sp-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Calcium / metabolism
  • Cell Differentiation*
  • Cells, Cultured
  • Glycosylation
  • Humans
  • Keratinocytes / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Protein Processing, Post-Translational
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism
  • Time Factors
  • Transcription, Genetic
  • Transfection
  • beta-N-Acetylhexosaminidases / genetics
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • Membrane Proteins
  • Protein Precursors
  • Sp1 Transcription Factor
  • SP1 protein, human
  • loricrin
  • involucrin
  • hexosaminidase C
  • beta-N-Acetylhexosaminidases
  • Calcium
  • Acetylglucosamine