Requirements for Interleukin 2 Promoter Transactivation by the Tax Protein of Human T-cell Leukemia Virus Type 1

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1996 Jul 1

PMID 8668173

Citations 5

Authors

V E Curtiss

R Smilde

K L McGuire

Affiliations

Soon will be listed here.

Abstract

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) upregulates the expression of several cellular genes by activating members of both the NF-kappaB and bZIP families of transcription factors. Recent studies demonstrate that the CD28 response element (CD28RE) of the interleukin 2 (IL-2) promoter is the site upregulated by Tax in stimulated T cells. Although some reports suggest that this site is transactivated by NF-kappaB family members, others disagree, leaving the identity of the transcription factor(s) binding the CD28RE unclear. The studies presented here further characterize the response of the IL-2 promoter and CD28RE to the HTLV-1 Tax protein and demonstrate that the TATA-proximal AP-1 binding site of the IL-2 promoter is also necessary for Tax transactivation in stimulated Jurkat cells. In contrast to its upregulation of the IL-2 promoter which requires T-cell stimulation, Tax transactivates the isolated CD28RE-AP-1 element without stimulation but is greatly synergized by calcium ionophore and phorbol ester. Additionally, transactivation of the IL-2 promoter requires the Tax activation domain involved in upregulation of bZIP-enhanced transcription while the NF-kappaB-activating domain of Tax is dispensable. Interestingly, both domains appear to be necessary for the activation of the isolated CD28RE-AP-1 sequence in the context of a heterologous promoter construct. This strongly suggests that activation of NF-kappaB is insufficient to activate transcription via the CD28RE-AP-1 element of the IL-2 promoter and that a different transcription factor, upregulated via the activation domain of the HTLV-1 Tax protein, may be involved.

Citing Articles

The HBZ-SP1 isoform of human T-cell leukemia virus type I represses JunB activity by sequestration into nuclear bodies.

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PMID: 17306025 PMC: 1805765. DOI: 10.1186/1742-4690-4-14.

Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template.

Lu H, Pise-Masison C, Fletcher T, Schiltz R, Nagaich A, Radonovich M Mol Cell Biol. 2002; 22(13):4450-62.

PMID: 12052856 PMC: 133924. DOI: 10.1128/MCB.22.13.4450-4462.2002.

Molecular interactions involved in the transactivation of the human T-cell leukemia virus type 1 promoter mediated by Tax and CREB-2 (ATF-4).

Gachon F, Thebault S, Peleraux A, Devaux C, Mesnard J Mol Cell Biol. 2000; 20(10):3470-81.

PMID: 10779337 PMC: 85640. DOI: 10.1128/MCB.20.10.3470-3481.2000.

Triple synergism of human T-lymphotropic virus type 1-encoded tax, GATA-binding protein, and AP-1 is required for constitutive expression of the interleukin-5 gene in adult T-cell leukemia cells.

Yamagata T, Mitani K, Ueno H, Kanda Y, Yazaki Y, Hirai H Mol Cell Biol. 1997; 17(8):4272-81.

PMID: 9234684 PMC: 232280. DOI: 10.1128/MCB.17.8.4272.

HTLV-I Tax self-association in optimal trans-activation function.

Jin D, Jeang K Nucleic Acids Res. 1997; 25(2):379-87.

PMID: 9016568 PMC: 146437. DOI: 10.1093/nar/25.2.379.

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