Activation of HTLV-I gene transcription by protein tyrosine phosphatase inhibitors. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Virology Année : 2004

Activation of HTLV-I gene transcription by protein tyrosine phosphatase inhibitors.

Résumé

Human T-cell leukemia virus type I (HTLV-I) transcription generally depends on the ability of the viral Tax protein to bind the CREB transcription factor and form an active complex by recruiting CBP/p300 coactivators to the long terminal repeat (LTR). Studies have demonstrated that T-cell activating agents that stimulate CREB are potent inducers of HTLV-I transcription. Herein, we demonstrate that bpV[pic], a protein tyrosine phosphatase (PTP) inhibitor activates the HTLV-I LTR in the presence and absence of Tax expression. Optimal activation occurred at 8 h and was synergistic with forskolin or PGE(2). Infected cell lines and cells transfected with HTLV-I proviral DNA were equally responsive to the synergistic effect of bpV and forskolin on HTLV-I gene expression. Activation of the LTR by bpV[pic] was T-cell receptor-independent, but required ZAP70, calcineurin activity and functional calcium entry. Inhibition of the SHP-1 PTP was suggested to be important. Transfection experiments with a CREB dominant-negative mutant and with isolated TRE1- or CREB-responsive reporter constructs and treatment with the MDL-12,330A adenylate cyclase inhibitor all supported the involvement of a CREB/ATF family member in this bpV-dependent activation of the HTLV-I LTR, although CREB itself did not seem to be involved. Analysis of HTLV-I reporter constructs containing mutated CREB-binding sites also implied the involvement of another element in this activation. These results demonstrate for the first time a powerful effect of PTP inhibitors on HTLV-I LTR activity and suggest participation of both CREB-dependent and -independent pathways in this activation.

Domaines

Virologie Cancer

Dates et versions

hal-00188427 , version 1 (16-11-2007)

Identifiants

Citer

Mélanie Langlois, Brigitte Audet, Eric Legault, Marie-Eve Paré, Michel Ouellet, et al.. Activation of HTLV-I gene transcription by protein tyrosine phosphatase inhibitors.. Virology, 2004, 329 (2), pp.395-411. ⟨10.1016/j.virol.2004.09.003⟩. ⟨hal-00188427⟩
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