Identification of protein-binding sequences mediating constitutive and 12-O-tetradecanoylphorbol-13-acetate-induced VL30 transcription in cultured mouse and human keratinocytes.

A retrovirus-like 30S (VL30) gene induced in mouse epidermis after a single application of 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as a model gene to define mechanisms of transcriptional regulation in keratinocytes. Sequences important for TPA and epidermal growth factor-induced transcription were found to be separated from eacho other within the long terminal repeat. Deletion mapping of the long terminal repeat region and linking short sequences to a heterologous promoter made it possible to identify a 28-base pair VL30 TPA-responsive element. VL30 TPA-responsive element mediated both basal and TPA-induced transcription in the mouse keratinocyte cell line Balb/MK and in normal human keratinocytes. Gel-retardation and transient transfection experiments indicated that two nuclear factors (VLX and VLY) bind independently to the VL30 TPA-responsive element in juxtaposed positions and that the binding sites collaborate functionally in constitutive and TPA-induced transcription. The sequence involved in VLY binding shows no homology to previously identified binding motifs. Two different sequences involved in mediating TPA-induced transcription of the urokinase plasminogen activator and of the c-jun gene, respectively, competed for proteins with affinity toward the VLX binding site. No competition was found with sequences containing the consensus AP-1 binding site.

• Publication year

  1991

• Venue

  Journal of Biological Chemistry

• Publication date

  1991-12-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0021-9258(18)54304-0PMID 1722214
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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