Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors.

Armstrong, Allison; Franklin, Audrey A.; Uittenbogaard, Martine; Giebler, Holli A.; Nyborg, Jennifer K.

doi:10.1073/pnas.90.15.7303

Cited by 117 publications

(115 citation statements)

References 31 publications

(32 reference statements)

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“…Analyses of Tax mutants have suggested that the NH 2 -terminal domain of Tax is important for CREB bZip (basic domain-leucine zipper) binding, while the midsection and the COOH terminus of Tax are important for subunit dimerization and possibly interaction with basal transcription factors, respectively (1,23,42,47). Several groups have also reported that Tax enhances the dimerization and DNA binding of bZip proteins in vitro (3,7,12,39,50,52).…”

mentioning

confidence: 99%

An Exposed KID-Like Domain in Human T-Cell Lymphotropic Virus Type 1 Tax Is Responsible for the Recruitment of Coactivators CBP/p300

Harrod

Tang

Nicot

et al. 1998

Molecular and Cellular Biology

169

236

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confidence: 99%

An Exposed KID-Like Domain in Human T-Cell Lymphotropic Virus Type 1 Tax Is Responsible for the Recruitment of Coactivators CBP/p300

Harrod

Tang

Nicot

et al. 1998

Molecular and Cellular Biology

169

236

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“…Interactions of Tax with members of the ATF/CREB family of transcription factors including CREB and CREM (3,7,62,71,78,80,86) and ATF-1 (3,80,86) have been demonstrated. Complex formation between Tax and ATF/CREB proteins results in increased binding affinity of these factors to the HTLV-1 21-bp repeats (7,13,62,80,84).…”

mentioning

confidence: 99%

Differential Transcriptional Activation by Human T-Cell Leukemia Virus Type 1 Tax Mutants Is Mediated by Distinct Interactions with CREB Binding Protein and p300

Bex

Yin

Burny³

et al. 1998

Molecular and Cellular Biology

117

104

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The human T-cell leukemia virus type 1 Tax protein transforms human T lymphocytes, which can lead to the development of adult T-cell leukemia. Tax transformation is related to its ability to activate gene expression via the ATF/CREB and the NF-B pathways. Transcriptional activation of these pathways is mediated by the actions of the related coactivators CREB binding protein (CBP) and p300. In this study, immunocytochemistry and confocal microscopy were used to localize CBP and p300 in cells expressing wild-type Tax or Tax mutants that are able to selectively activate gene expression from either the NF-B or ATF/CREB pathway. Wild-type Tax colocalized with both CBP and p300 in nuclear bodies which also contained ATF-1 and the RelA subunit of NF-B. However, a Tax mutant that selectively activates gene expression from only the ATF/CREB pathway colocalized with CBP but not p300, while a Tax mutant that selectively activates gene expression from only the NF-B pathway colocalized with p300 but not CBP. In vitro and in vivo protein interaction studies indicated that the integrity of two independent domains of Tax delineated by these mutants was involved in the direct interaction of Tax with either CBP or p300. These studies are consistent with a model in which activation of either the NF-B or the ATF/CREB pathway by specific Tax mutants is mediated by distinct interactions with related coactivator proteins.The human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus which is the etiologic agent of adult T-cell leukemia (36,51,65). Adult T-cell leukemia is characterized by the presence in the peripheral blood of malignant lymphoid cells which contain the HTLV-1 provirus (38, 85). HTLV-1 encodes a protein, Tax, which is a potent activator of viral transcription (15,22,77) and is also involved in transforming cells of both lymphoid and nonlymphoid origin (30,31,54,66,76,79). Tax also activates the expression of specific cellular genes involved in normal T-cell activation and proliferation, including the gene coding for interleukin-2, the gene for interleukin-2 receptor, and the proto-oncogene c-fos (5,23,46,72). These latter patterns of transcriptional activation result from Tax-mediated increases in the nuclear levels of 37,41,42,45,50) and direct interactions of Tax with the serum response factor (24).Tax activates HTLV-1 gene expression via direct interactions with members of the ATF/CREB family of transcription factors, which bind to three 21-bp repeat regulatory elements present in the viral long terminal repeat (LTR) (12,25,26,33,58,60,62,71,80,83,84,86). Interactions of Tax with members of the ATF/CREB family of transcription factors including CREB and CREM (3,7,62,71,78,80,86) and 80,86) have been demonstrated. Complex formation between Tax and ATF/CREB proteins results in increased binding affinity of these factors to the HTLV-1 21-bp repeats (7,13,62,80,84). However, a more complex set of interactions is probably required for Tax activation of gene expression. The binding of Tax to the cellular coactivator CRE...

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“…Tax interacts with certain cellular transcription factors which bind the elements through which Tax function is mediated (8,23,69,70,74,75) nuclear protein with limited transactivation potential unless posttranslationally activated through a cAMP-responsive pathway (73). Tax has also been reported to exert its effects by enhancing the dimerization efficiency of many (if not all) DNA-binding proteins of the basic-leucine zipper class, including CREB (3,71,75).NF-KB is a family of dimeric transcription factor complexes, composed by many combinations of members of the RelV NF-KB family of polypeptides, including, in vertebrates, p50, p52 (p5OB, p49, lyt-10), RelA (p65), and RelB (reviewed in references 13,29,and 30). The predominant complex in most cells is p5O/p65 (p50/ReIA).…”

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confidence: 99%

mentioning

confidence: 99%

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Kinetic analysis of human T-cell leukemia virus type I Tax-mediated activation of NF-kappa B.

Kanno¹,

Brown²,

Franzoso³

et al. 1994

Mol. Cell. Biol.

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The human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of cellular genes, at least in part, by activating the endogenous NF-KB transcription factors. Induced expression of cellular genes is thought to be important for transformation of T cells to continued growth, a prelude to the establishment of adult T-cell leukemia. However, neither underlying mechanisms nor kinetics of the Tax-mediated activation of NF-KB are understood. We have analyzed a permanently transfected Jurkat T-cell line in which the expression of Tax is entirely dependent on addition of heavy metals. The initial NF-K.B binding activity seen after induction of Tax is due almost exclusively to p5O/p65 heterodimers. At later times, NF-KB complexes containing c-Rel and/or p52 accumulate. The early activation of p5O/p65 complexes is a posttranslational event, since neither mRNA nor protein levels of NF-KB subunits had increased at that time. We demonstrate for the first time a Tax-induced proteolytic degradation of the NF-KB inhibitor, IKcB-oa, which may trigger the initial nuclear translocation of NF-K.B. As nuclear NF-KB rapidly and potently stimulates resynthesis of IKB-a, the steady-state level of IKB-a does not significantly change. Thus, the dramatic Tax-induced increase in the IKB-a turnover may continually weaken inhibition and activate NF-KB. Additional, distinct actions of Tax may contribute further to the high levels of NF-KB activity seen.Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent for adult T-cell leukemia (reviewed in reference 66). Along with standard retroviral genes coding for Gag, Pol, and Env, the pX region of the HTLV-I genome encodes several unique products, including the Tax protein. Tax is essential for viral gene expression, mediating its effects on transcription through cyclic AMP (cAMP)-responsive elements (CRE) in the viral long terminal repeat (LTR) (36).Several lines of evidence indicate that Tax is essential also for initiation of cellular transformation by 54). Tax is known to induce many cellular growth-promoting genes, including genes encoding the T-cell growth factor interleukin-2 (IL-2) (34), the a subunit of the IL-2 receptor (4,43,57), and the c-fos proto-oncogene (22). Also, Tax can induce expression from the LTR of human immunodeficiency virus type 1 (HIV-1) in dually infected cells (10).The activation of cellular and viral genes by Tax is mediated through at least three distinct cis-acting DNA sites: CRE (e.g., those present in the HTLV-I LTR and in the c-fos promoter), serum-responsive elements (e.g., that present in the c-fos promoter), and KB elements (e.g., those present in the IL-2 and IL-2 receptor a-subunit promoters and in the HIV-1 LTR). Distinct domains of Tax are important for activation through CRE and KB sites, as revealed by mutational analysis (64, 65); this finding suggests distinct mechanisms of action. While Tax does not bind to DNA directly on its own, it does harbor potential transactivation domains (24). Tax interacts with certain cellular...

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Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors.

Abstract: The Tax protein, encoded by the human

Cited by 117 publications

References 31 publications

An Exposed KID-Like Domain in Human T-Cell Lymphotropic Virus Type 1 Tax Is Responsible for the Recruitment of Coactivators CBP/p300

An Exposed KID-Like Domain in Human T-Cell Lymphotropic Virus Type 1 Tax Is Responsible for the Recruitment of Coactivators CBP/p300

Differential Transcriptional Activation by Human T-Cell Leukemia Virus Type 1 Tax Mutants Is Mediated by Distinct Interactions with CREB Binding Protein and p300

Kinetic analysis of human T-cell leukemia virus type I Tax-mediated activation of NF-kappa B.

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