Interaction between C/EBPbeta and Tax down-regulates human T-cell leukemia virus type I transcription. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Virology Année : 2004

Interaction between C/EBPbeta and Tax down-regulates human T-cell leukemia virus type I transcription.

Résumé

The human T-cell leukemia virus type I (HTLV-I) Tax protein trans-activates viral transcription through three imperfect tandem repeats of a 21-bp sequence called Tax-responsive element (TxRE). Tax regulates transcription via direct interaction with some members of the activating transcription factor/CRE-binding protein (ATF/CREB) family including CREM, CREB, and CREB-2. By interacting with their ZIP domain, Tax stimulates the binding of these cellular factors to the CRE-like sequence present in the TxREs. Recent observations have shown that CCAAT/enhancer binding protein beta (C/EBPbeta) forms stable complexes on the CRE site in the presence of CREB-2. Given that C/EBPbeta has also been found to interact with Tax, we analyzed the effects of C/EBPbeta on viral Tax-dependent transcription. We show here that C/EBPbeta represses viral transcription and that Tax is no more able to form a stable complex with CREB-2 on the TxRE site in the presence of C/EBPbeta. We also analyzed the physical interactions between Tax and C/EBPbeta and found that the central region of C/EBPbeta, excluding its ZIP domain, is required for direct interaction with Tax. It is the first time that Tax is described to interact with a basic leucine-zipper (bZIP) factor without recognizing its ZIP domain. Although unexpected, this result explains why C/EBPbeta would be unable to form a stable complex with Tax on the TxRE site and could then down-regulate viral transcription. Lastly, we found that C/EBPbeta was able to inhibit Tax expression in vivo from an infectious HTLV-I molecular clone. In conclusion, we propose that during cell activation events, which stimulate the Tax synthesis, C/EBPbeta may down-regulate the level of HTLV-I expression to escape the cytotoxic-T-lymphocyte response.

Domaines

Virologie Cancer

Dates et versions

hal-00188432 , version 1 (16-11-2007)

Identifiants

Citer

Patrick Hivin, Gilles Gaudray, Christian Devaux, Jean-Michel Mesnard. Interaction between C/EBPbeta and Tax down-regulates human T-cell leukemia virus type I transcription.. Virology, 2004, 318 (2), pp.556-65. ⟨10.1016/j.virol.2003.10.027⟩. ⟨hal-00188432⟩
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