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Journal of Virology, October 1998, p. 8332-8337, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

CREB-2, a Cellular CRE-Dependent Transcription Repressor, Functions in Association with Tax as an Activator of the Human T-Cell Leukemia Virus Type 1 Promoter

Frederic Gachon, Annick Peleraux, Sabine Thebault, Joelle Dick,dagger Isabelle Lemasson, Christian Devaux, and Jean-Michel Mesnard*

Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CRBM-CNRS UPR 1086, Institut de Biologie, 34060 Montpellier, France

Received 27 March 1998/Accepted 16 June 1998

The Tax protein of the human T-cell leukemia virus type 1 (HTLV-1) has been implicated in human T-cell immortalization. The primary function of Tax is to transcriptionally activate the HTLV-1 promoter, but Tax is also known to stimulate expression of cellular genes. It has been reported to associate with several transcription factors, as well as proteins not involved in transcription. To better characterize potential cellular targets of Tax present in infected cells, a Saccharomyces cerevisiae two-hybrid screening was performed with a cDNA library constructed from the HTLV-1-infected MT2 cell line. From this study, we found 158 positive clones representing seven different cDNAs. We focused our attention on the cDNA encoding the transcription factor CREB-2. CREB-2 is an unconventional member of the ATF/CREB family in that it lacks a protein kinase A (PKA) phosphorylation site and has been reported to negatively regulate transcription from the cyclic AMP response element of the human enkephalin promoter. In this study, we demonstrate that CREB-2 cooperates with Tax to enhance viral transcription and that its basic-leucine zipper C-terminal domain is required for both in vitro and in vivo interactions with Tax. Our results confirm that the activation of the HTLV-1 promoter through Tax and factors of the ATF/CREB family is PKA independent.

* Corresponding author. Mailing address: Laboratoire Infections Rétrovirales et Signalisation Cellulaire, Institut de Biologie, 4 Blvd. Henri IV, 34060 Montpellier, France. Phone: (33) 4 67 60 86 60. Fax: (33) 4 67 60 44 20. E-mail: mesnard{at}crbm.cnrs-mop.fr.

dagger Present address: Heymans Institute of Pharmacology, University of Ghent Medical School, 9000 Ghent, Belgium.

Journal of Virology, October 1998, p. 8332-8337, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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