B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and Fos

Oncogene. 2000 Mar 30;19(14):1752-63. doi: 10.1038/sj.onc.1203491.


B-ATF is a nuclear basic leucine zipper protein that belongs to the AP-1/ATF superfamily of transcription factors. Northern blot analysis reveals that the human B-ATF gene is expressed most highly in hematopoietic tissues. Interaction studies in vitro and in vivo show that the leucine zipper of B-ATF mediates dimerization with members of the Jun family of proteins. Chimeric proteins consisting of portions of B-ATF and the DNA binding domain of the yeast activator GAL4 do not stimulate reporter gene expression in mammalian cells, indicating that B-ATF does not contain a conventional transcription activation domain. Jun/B-ATF dimers display similar DNA binding profiles as Jun/Fos dimers, with a bias toward binding TRE (12-O-tetradecanolyphorbol-13-acetate-response element) over CRE (cyclic AMP-response element) DNA sites. B-ATF inhibits transcriptional activation of a reporter gene containing TRE sites in a dose-dependent manner, presumably by competing with Fos for Jun and forming transcriptionally inert Jun/B-ATF heterodimers. Stable expression of B-ATF in C3H10T1/2 cells does not reduce cell viability, but does result in a reduced cellular growth rate when compared to controls. This effect is dominant in the presence of the growth promoting effects of the H-Ras or the v-Fos oncoproteins, since expression of B-ATF restricts the efficiency of focus formation by these transforming agents. These findings demonstrate that B-ATF is a tissue-specific transcription factor with the potential to function as a dominant-negative to AP-1.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Basic-Leucine Zipper Transcription Factors
  • Binding Sites
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Consensus Sequence
  • DNA-Binding Proteins*
  • Dimerization
  • Gene Expression
  • Hematopoietic System / metabolism
  • Humans
  • Leucine Zippers*
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oncogene Protein p21(ras) / genetics*
  • Oncogene Proteins v-fos / genetics*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism
  • RNA, Messenger
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Response Elements
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transcriptional Activation*
  • Tumor Cells, Cultured


  • BATF protein, human
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Oncogene Proteins v-fos
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • Oncogene Protein p21(ras)