Specific members of the Jun protein family regulate collagenase expression in response to various extracellular stimuli

Matrix Suppl. 1992;1:156-64.

Abstract

The transcription factor AP1 which regulates expression of collagenase in response to various extracellular signals is a multimeric complex composed of members of the Jun- and Fos families. To examine the biological role of the various components in signal transduction we analyzed the expression of two of them (cJun, JunB) and collagenase in response to phorbol esters, cAMP and TGF-beta. While all three genes are induced by phorbol ester and TGF-beta only JunB is induced by cAMP. In contrast expression of cJun and collagenase is reduced by cAMP indicating that cJun and JunB are not coordinately regulated. In addition JunB is not an efficient activator of the cJun and collagenase promoters although both cJun and JunB exhibit similar DNA binding properties, indicating that the differences in biological activity is due to differences in their activation domains. Our results imply that enhanced expression of collagenase (and cJun) depends on the activation of cJun. Expression of cJun and collagenase is inhibited under certain conditions of high levels of JunB. This suggests a negative regulatory function of JunB which greatly expands the potential of the Jun protein family in changing the transcription of specific genes involved in triggering complex biological processes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Colforsin / pharmacology
  • Collagenases / biosynthesis*
  • Cyclic AMP / physiology
  • DNA, Neoplasm / metabolism
  • Enzyme Induction / drug effects
  • Gene Expression Regulation / drug effects
  • Genes, fos
  • Genes, jun
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Promoter Regions, Genetic
  • Protein Multimerization
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / physiology
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Proto-Oncogene Proteins c-jun / physiology*
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transforming Growth Factor beta
  • Colforsin
  • Cyclic AMP
  • Collagenases
  • Tetradecanoylphorbol Acetate