Redistribution of transcription factor AP-2α in differentiating cultured human epidermal cells

Olga M. Mazina, Marjorie A. Phillips, Trevor Williams, Carol A. Vines, Gary N. Cherr, Robert H. Rice

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Expression of the transcription factor AP-2α was examined in cultured human epidermal cells. Levels of AP-2α mRNA increased substantially after the cultures reached confluence, similar to the expression pattern of the differentiation markers involucrin and keratinocyte transglutaminase. The level of AP-2α protein in nuclear extracts declined markedly after confluence, however, along with its ability to form complexes with oligonucleotides containing the AP-2 response element. In contrast, the levels of AP-2α protein in cytoplasmic extracts increased dramatically after confluence, but these extracts had low DNA binding activity. Supershift experiments with specific antisera detected only AP-2α and not the β or γ isoforms. Examination of its localization by confocal microscopy revealed that AP-2α was primarily in the nucleus of basal cells and largely cytoplasmic in the most superficial cells. Localization was a dynamic phenomenon in that changing the medium resulted in accumulation of this transcription factor in the nucleus after several hours. Overall, the data indicate that AP-2α transcriptional activity is regulated in a differentiation-dependent manner in cultured keratinocytes and that this occurs by relocalization of the protein. Nuclear localization of the AP-2α protein in basal cells permits its accessibility to response elements in gene promoters, whereas sequestration in the cytoplasm as the differentiation program progresses curtails its transcriptional activity. This regulatory scheme may provide keratinocytes with the ability to restore AP-2 transcriptional activity rapidly by redistribution to the nucleus after receiving an appropriate growth signal, such as a medium change.

Original languageEnglish (US)
Pages (from-to)864-870
Number of pages7
JournalJournal of Investigative Dermatology
Volume117
Issue number4
DOIs
StatePublished - 2001

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Transcription Factor AP-2
Keratinocytes
Response Elements
Proteins
Transglutaminases
Differentiation Antigens
Cells
Nuclear Proteins
Basal Ganglia
Cell Nucleus
Confocal Microscopy
Oligonucleotides
Immune Sera
Confocal microscopy
Protein Isoforms
Cytoplasm
Transcription Factors
Messenger RNA
Genes
DNA

Keywords

  • Growth
  • Involucrin
  • SCC-9
  • Stratification
  • TGM1

ASJC Scopus subject areas

  • Dermatology

Cite this

Redistribution of transcription factor AP-2α in differentiating cultured human epidermal cells. / Mazina, Olga M.; Phillips, Marjorie A.; Williams, Trevor; Vines, Carol A.; Cherr, Gary N.; Rice, Robert H.

In: Journal of Investigative Dermatology, Vol. 117, No. 4, 2001, p. 864-870.

Research output: Contribution to journalArticle

Mazina, Olga M. ; Phillips, Marjorie A. ; Williams, Trevor ; Vines, Carol A. ; Cherr, Gary N. ; Rice, Robert H. / Redistribution of transcription factor AP-2α in differentiating cultured human epidermal cells. In: Journal of Investigative Dermatology. 2001 ; Vol. 117, No. 4. pp. 864-870.
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