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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. 2000 Mar 30; 19(14):1752-63.O

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.

Authors+Show Affiliations

Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10777209

Citation

Echlin, D R., et al. "B-ATF Functions as a Negative Regulator of AP-1 Mediated Transcription and Blocks Cellular Transformation By Ras and Fos." Oncogene, vol. 19, no. 14, 2000, pp. 1752-63.
Echlin DR, 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. 2000;19(14):1752-63.
Echlin, D. R., Tae, H. J., Mitin, N., & Taparowsky, E. J. (2000). B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and Fos. Oncogene, 19(14), 1752-63.
Echlin DR, et al. 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. PubMed PMID: 10777209.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and Fos. AU - Echlin,D R, AU - Tae,H J, AU - Mitin,N, AU - Taparowsky,E J, PY - 2000/4/25/pubmed PY - 2000/6/10/medline PY - 2000/4/25/entrez SP - 1752 EP - 63 JF - Oncogene JO - Oncogene VL - 19 IS - 14 N2 - 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. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/10777209/B_ATF_functions_as_a_negative_regulator_of_AP_1_mediated_transcription_and_blocks_cellular_transformation_by_Ras_and_Fos_ L2 - https://doi.org/10.1038/sj.onc.1203491 DB - PRIME DP - Unbound Medicine ER -