A specific lysine in c-Jun is required for transcriptional repression by E1A and is acetylated by p300

EMBO J. 2001 Nov 1;20(21):6095-103. doi: 10.1093/emboj/20.21.6095.

Abstract

The adenovirus E1A protein regulates transcription of cellular genes via its interaction with the transcriptional coactivators p300/CBP. The collagenase promoter activated by the c-Jun protein is repressed by E1A. Here we show that E1A repression is specific for c-Jun, as E1A does not repress the collagenase promoter activated by the homologous transcription factor EB1. Using chimeras of c-Jun and EB1, we demonstrate that a 12 amino acid region in the basic region of the c-Jun DNA-binding domain is essential for repression by E1A. Since repression requires the binding of p300 to E1A, we studied the involvement of p300 acetyltransferase activity in the repression mechanism. We demonstrate that c-Jun is acetylated in vivo, and mutational analysis identified Lys271 in the c-Jun basic region to be essential for repression of the collagenase promoter by E1A. In addition, Lys271 is acetylated both in vitro and in vivo. These results suggest that the specific repression of the collagenase promoter by E1A involves acetylation of c-Jun.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Adenovirus E1A Proteins / metabolism*
  • Adenovirus E1A Proteins / pharmacology
  • Amino Acid Substitution
  • Animals
  • Carcinogens / pharmacology
  • Cell Line
  • Collagenases / biosynthesis
  • Collagenases / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / physiology
  • E1A-Associated p300 Protein
  • Enzyme Induction / drug effects
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Lysine / physiology
  • Mice
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mutagenesis, Site-Directed
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / metabolism
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism
  • Repressor Proteins / pharmacology
  • Retina / cytology
  • Retina / drug effects
  • Retina / embryology
  • Retina / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection
  • Viral Proteins*

Substances

  • Adenovirus E1A Proteins
  • BZLF1 protein, Herpesvirus 4, Human
  • Carcinogens
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trans-Activators
  • Viral Proteins
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Collagenases
  • Lysine
  • Tetradecanoylphorbol Acetate