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Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription

D Bohmann1, T J Bos, A Admon

  • 1Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley, CA 94720.

Science (New York, N.Y.)
|December 4, 1987
PubMed

Insights

The human proto-oncogene c-jun encodes a protein that binds DNA sequences, similar to the transcription factor AP-1. This discovery links c-jun to gene regulation and cancer development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Nuclear oncogene products can alter gene regulation, potentially causing cancer.
  • The precise mechanisms of nuclear oncoprotein action are not fully understood.
  • The oncogene v-jun shares homology with the DNA-binding domain of yeast transcription factor GCN4, which recognizes similar DNA sequences as AP-1.

Purpose of the Study:

  • To investigate the relationship between the human proto-oncogene c-jun and the enhancer binding protein AP-1.
  • To determine if the c-jun product directly interacts with DNA sequences to regulate gene expression.

Main Methods:

  • Isolation and cloning of the human proto-oncogene c-jun.
  • Bacterial expression of cloned c-jun to produce the protein.
  • Generation of antibodies against v-jun peptides for cross-reactivity testing with human AP-1.
  • Partial amino acid sequencing of purified AP-1.

Main Results:

  • The deduced amino acid sequence of c-jun showed over 80% identity with v-jun.
  • Bacterial expression of c-jun yielded a protein with DNA-binding properties identical to AP-1.
  • Antibodies against v-jun peptides specifically reacted with human AP-1.
  • Partial sequencing of AP-1 revealed shared tryptic peptides with the c-jun protein.

Conclusions:

  • The structural and functional similarities strongly suggest that AP-1 is encoded by c-jun.
  • The c-jun proto-oncogene product directly binds specific DNA sequences to regulate gene expression.
  • This finding enables the identification of genes controlled by c-jun that influence cell growth and neoplasia.

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