A short region containing an AP-1 binding site is essential for transforming growth factor-beta-induced c-jun gene expression in osteoblastic cells

IUBMB Life. 2000 Mar;49(3):229-34. doi: 10.1080/713803612.

Abstract

Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory peptide that elicits different responses in different cell types. Much remains unknown about the pathway of intracellular TGF-beta signal transduction, but TGF-beta is known to induce expression of several genes by way of the transcription factor AP-1. We studied the mechanism that mediates TGF-beta-induced gene expression of c-jun, a component of AP-1, in MC3T3-E1 osteoblastic cells. To map in detail the corresponding responsive elements in the rat c-jun promoter, we generated a series of 5' deletion promoter/luciferase reporter gene constructs. Transient cell transfection assays identified the region located between positions -79 and -59 as being critical for the TGF-beta response and for the basal activity of the promoter. Gel mobility shift assays indicated specific binding of nuclear proteins to this 21-bp region of the c-jun promoter containing an AP-1 binding site. These results show that the AP-1-dependent mechanism is involved in TGF-beta-induced increase of c-jun induction, suggesting positive autoregulation of AP-1.

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites
  • Cell Nucleus / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Gene Deletion
  • Genes, jun / genetics*
  • Mice
  • Models, Genetic
  • Mutagenesis, Site-Directed
  • Osteoblasts / metabolism*
  • Plasmids / metabolism
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Rats
  • Signal Transduction
  • Transcription Factor AP-1 / metabolism*
  • Transfection
  • Transforming Growth Factor beta / metabolism*

Substances

  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Transforming Growth Factor beta