Distinct functional interactions of human Skn-1 isoforms with Ese-1 during keratinocyte terminal differentiation.
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.
Cabral
Adriana
A
Laboratory of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, P. O. Box 9502, 2300 RA Leiden, The Netherlands.
Fischer
David F
DF
Vermeij
Wilbert P
WP
Backendorf
Claude
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D015723:Gene Library; D006801:Humans; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D050810:Octamer Transcription Factors; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D051381:Rats; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D050810:Octamer Transcription Factors; C080533:Pou2f3 protein, rat; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase