B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and Fos.
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.
Echlin
D R
DR
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.
Tae
H J
HJ
Mitin
N
N
Taparowsky
E J
EJ
D000328:Adult; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016384:Consensus Sequence; D004268:DNA-Binding Proteins; D019281:Dimerization; D015870:Gene Expression; D006413:Hematopoietic System / Q000378:metabolism; D006801:Humans; D016350:Leucine Zippers; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D016761:Oncogene Proteins v-fos / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
C099359:BATF protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016761:Oncogene Proteins v-fos; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D015689:Oncogene Protein p21(ras)