Distinct functional interactions of human Skn-1 isoforms with Ese-1 during keratinocyte terminal differentiation

J Biol Chem. 2003 May 16;278(20):17792-9. doi: 10.1074/jbc.M300508200. Epub 2003 Mar 6.


Among the three major POU proteins expressed in human skin, Oct-1, Tst-1/Oct-6, and Skn-1/Oct-11, only the latter induced SPRR2A, a marker of keratinocyte terminal differentiation. In this study, we have identified three Skn-1 isoforms, which encode proteins with various N termini, generated by alternative promoter usage. These isotypes showed distinct expression patterns in various skin samples, internal squamous epithelia, and cultured human keratinocytes. Skn-1a and Skn-1d1 bound the SPRR2A octamer site with comparable affinity and functioned as transcriptional activators. Skn-1d2 did not affect SPRR2A expression. Skn-1a, the largest protein, functionally cooperated with Ese-1/Elf-3, an epithelial-specific transcription factor, previously implicated in SPRR2A induction. This cooperativity, which depended on an N-terminal pointed-like domain in Skn-1a, was not found for Skn-1d1. Actually, Skn-1d1 counteracted the cooperativity between Skn-1a and Ese-1. Apparently, the human Skn-1 locus encodes multifunctional protein isotypes, subjected to biochemical cross-talk, which are likely to play a major role in the fine-tuning of keratinocyte terminal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cells, Cultured
  • Chloramphenicol O-Acetyltransferase / metabolism
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins*
  • Dose-Response Relationship, Drug
  • Gene Library
  • Humans
  • In Situ Hybridization
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Luciferases / metabolism
  • Mice
  • Molecular Sequence Data
  • Octamer Transcription Factors
  • Plasmids / metabolism
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins*
  • Rats
  • Repressor Proteins / chemistry*
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Time Factors
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured


  • DNA, Complementary
  • DNA-Binding Proteins
  • ELF3 protein, human
  • Octamer Transcription Factors
  • Pou2f3 protein, rat
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Luciferases
  • Chloramphenicol O-Acetyltransferase