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J. Biol. Chem., Vol. 278, Issue 20, 17792-17799, May 16, 2003
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From the Laboratory of Molecular Genetics, Leiden Institute of
Chemistry, Leiden University, P. O. Box 9502, 2300 RA Leiden, The Netherlands
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.
Distinct Functional Interactions of Human Skn-1 Isoforms with
Ese-1 during Keratinocyte Terminal Differentiation*
,
§,
*
This work was supported by the J. A. Cohen Institute
(Leiden) and by European Community Grant BMH4-CT96-0319.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These authors contributed equally to this work.
§
Present address: Netherlands Institute for Brain Research,
Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands.
¶
To whom correspondence should be addressed: Laboratory of
Molecular Genetics, Gorlaeus Laboratories, P. O. Box 9502, 2300 RA
Leiden, The Netherlands. Tel.: 31-71-527-4409; Fax: 31-71-527-4537; E-mail: backendo@chem.leidenuniv.nl.
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