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Molecular and Cellular Biology, May 2000, p. 3470-3481, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)

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

Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS EP 2104, Institut de Biologie, 34060 Montpellier, France

Received 29 November 1999/Returned for modification 5 January 2000/Accepted 29 February 2000

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.

* Corresponding author. Mailing address: Laboratoire Infections Rétrovirales et Signalisation Cellulaire, Institut de Biologie, 4 Bd 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: Département d'Immuno-oncologie, Sanofi-Synthélabo, 34184 Montpellier cedex 4, France.

Molecular and Cellular Biology, May 2000, p. 3470-3481, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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