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

Adriana Cabral, David F Fischer, Wilbert P Vermeij, Claude Backendorf

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)17792-9
Number of pages8
JournalThe Journal of biological chemistry
Volume278
Issue number20
DOIs
Publication statusPublished - 16 May 2003
Externally publishedYes

Keywords

  • 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
  • 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
  • Proto-Oncogene Proteins c-ets
  • Rats
  • Repressor Proteins/chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Time Factors
  • Trans-Activators/chemistry
  • Transcription Factors/metabolism
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured

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