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

Oncogene volume 19, pages 1752–1763 (2000)Cite this article

Abstract

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.

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Acknowledgements

The authors thank all of the members of the EJ Taparowsky and S Konieczny laboratories at Purdue for their assistance during the course of this study. This work was supported by a grant awarded to EJ Taparowsky from the National Cancer Institute (CA-78264) and a predoctoral fellowship awarded to DR Echlin from the US Army Breast Cancer Research Program.

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Author notes

  1. Deborah R Echlin

    Present address: Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, 60637, IL, USA

  2. Hyi-Jeong Tae

    Present address: Biotechnology Research Institute, LG Chemical Ltd., 104-1 Munji-dong, Yusung, 305-380, Taejon, South Korea

  3. Deborah R Echlin and Hyi-Jeong Tae: DR Echlin and H-J Tae to be treated as co-first authors

Authors and Affiliations

  1. Department of Biological Sciences, Purdue University, West Lafayette, 47907-1392, Indiana, IN, USA

    Natalia Mitin & Elizabeth J Taparowsky

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  4. Elizabeth J Taparowsky
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Echlin, D., Tae, HJ., Mitin, N. et al. B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and Fos. Oncogene 19, 1752–1763 (2000). https://doi.org/10.1038/sj.onc.1203491

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