AP-2α: A Regulator of EGF Receptor Signaling and Proliferation in Skin Epidermis

AP-2 transcription factors have been implicated in epidermal biology, but their functional significance has remained elusive. Using conditional knockout technology, we show that AP-2α is essential for governing the balance between growth and differentiation in epidermis. In vivo, epidermis lacking A...

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Bibliographic Details
Published in:The Journal of cell biology 2006-01, Vol.172 (3), p.409-421
Main Authors: Xuan Wang, Bolotin, Diana, David H. Chu, Polak, Lisa, Williams, Trevor, Fuchs, Elaine
Format: Article
Language:English
Subjects:
Antibodies
Epidermal cells
Epidermis
Genes
Keratinocytes
Messenger RNA
Mice
Receptors
Skin
Transcription factors
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Summary:AP-2 transcription factors have been implicated in epidermal biology, but their functional significance has remained elusive. Using conditional knockout technology, we show that AP-2α is essential for governing the balance between growth and differentiation in epidermis. In vivo, epidermis lacking AP-2α exhibits elevated expression of the epidermal growth factor receptor (EGFR) in the differentiating layers, resulting in hyper-proliferation when the receptors are activated. Chromatin immunoprecipitation and promoter activity assays identify EGFR as a direct target gene for AP-2α repression, and, in the absence of AP-2α, this is manifested primarily in excessive EGF-dependent phosphoinositol-3 kinase/Akt activity. Together, our findings unveil a hitherto unrecognized repressive role for AP-2α in governing EGFR gene transcription as cells exit the basal layer and withdraw from the cell cycle. These results provide insights into why elevated AP-2α levels are often associated with terminal differentiation and why tumor cells often display reduced AP-2α and elevated EGFR proteins.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200510002