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A murine ATFa-associated factor with transcriptional repressing activity

Oncogene volume 19, pages 1807–1819 (2000)Cite this article

Abstract

The ATFa proteins, which are members of the CREB/ATF family of transcription factors, have previously been shown to interact with the adenovirus E1a oncoprotein and to mediate its transcriptional activity; they heterodimerize with Jun, Fos or related transcription factors, possibly altering their DNA-binding specificity; they also stably bind JNK2, a stress-induced protein kinase. Here we report the identification and characterization of a novel protein isolated in a yeast two-hybrid screen using the N-terminal half of ATFa as a bait. This 1306-residue protein (mAM, for mouse ATFa-associated Modulator) is rather acidic (pHi 4.5) and contains high proportions of Ser/Thr (21%) and Pro (11%) residues. It colocalizes and interacts with ATFa in mammalian cells, contains a bipartite nuclear localization signal and possesses an ATPase activity. Transfection experiments show that mAM is able to downregulate transcriptional activity, in an ATPase-independent manner. Our results indicate that mAM interacts with several components of the basal transcription machinery (TFIIE and TFIIH), including RNAPII itself. Together, these findings suggest that mAM may be involved in the fine-tuning of ATFa-regulated gene expression, by interfering with the assembly or stability of specific preinitiation transcription complexes.

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Abbreviations

ATF:

activating transcription factor

CAT:

chloramphenicol acetyl transferase

CREB:

cAMP responsive element binding protein

GSH:

glutathione

GST:

glutathione S-transferase

GTFs:

general transcription factors

HA:

hemagglutinin

JNK2:

c-Jun N-terminal-associated Kinase 2

NLS:

nuclear localisation signal

RNAPII:

RNA polymerase II

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Acknowledgements

We thank J Acker, H Boeuf, P Dollé, J-M Egly, J-M Garnier, R Gopalkrishnan, Y Lutz, M Rosa-Calatrava, Y Shaul and M Vigneron for gift of materials and helpful discussions. We are grateful to C Hauss for technical assistance, to I Kolb-Cheynel for production of recombinant baculoviruses, to J-L Vonesh for confocal microscopy, to the staffs of the cell culture, nucleotide sequencing and oligonucleotide synthesis, and artwork facilities for providing help and material. This work was supported by the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer, the Ligue Nationale contre le Cancer, the Hôpital Universitaire and the Université Louis Pasteur of Strasbourg.

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  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP 67400 Illkirch, Communauté Urbaine de Strasbourg, France

    Fabienne De Graeve, Anne Bahr, Bruno Chatton & Claude Kedinger

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  1. Fabienne De Graeve
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  2. Anne Bahr
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  3. Bruno Chatton
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De Graeve, F., Bahr, A., Chatton, B. et al. A murine ATFa-associated factor with transcriptional repressing activity. Oncogene 19, 1807–1819 (2000). https://doi.org/10.1038/sj.onc.1203492

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