CCAAT/enhancer-binding proteins. A role in regulation of human involucrin promoter response to phorbol ester

Chapla Agarwal, Tatiana Efimova, Jean F. Welter, James F. Crish, Richard L. Eckert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent inducer of keratinocyte differentiation and of involucrin gene expression. In the present study we show that a CCAAT/enhancer-binding protein (C/EBP) site in the proximal regulatory region is required for the phorbol ester response. Mutation of the C/EBP site results in the loss of basal and TPA-responsive activity. Gel mobility supershift analysis shows that C/EBPα binding to this site is increased by TPA treatment. Moreover, cotransfection of the human involucrin reporter plasmid with C/EBPα increases promoter activity to an extent comparable with TPA treatment. Mutation of the C/EBP-binding site eliminates these responses. Transfection experiments using GADD153 to create C/EBP-null conditions confirm that C/EBP factors are absolutely required for promoter activity and TPA responsiveness. C/EBPβ and C/EBPδ inhibit both TPA- and C/EBPα-dependent promoter activation, indicating functional differences among C/EBP family members. These results suggest that C/EBP transcription factor activity is necessary for basal promoter activity and TPA response of the involucrin gene.

Original languageEnglish (US)
Pages (from-to)6190-6194
Number of pages5
JournalJournal of Biological Chemistry
Issue number10
StatePublished - Mar 5 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'CCAAT/enhancer-binding proteins. A role in regulation of human involucrin promoter response to phorbol ester'. Together they form a unique fingerprint.

Cite this