The trans-activator tax of human T-cell leukemia virus type 1 (HTLV-1) interacts with cAMP-responsive element (CRE) binding and CRE modulator proteins that bind to the 21-base-pair enhancer of HTLV-1.

Suzuki, Takeshi; Fujisawa, Jun–ichi; Toita, Masami; Yoshida, Mitsuaki

doi:10.1073/pnas.90.2.610

Cited by 251 publications

(199 citation statements)

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“…on May 11, 2018 by guest http://jvi.asm.org/ activate transcription via CREB/ATF sites is context specific since at other CREB binding sites (i.e., those found in cellular promoters), Tax-CREB complex formation may occur (46,59,77), but no activation is seen. The above CycA-luc, DPA-luc, and CycD3-luc results are compatible with an alternative functional interpretation: Tax-CREB interaction at some TATAless promoters manifests as repression.…”

Section: Vol 75 2001mentioning

confidence: 99%

“…In ts13 cells, it has been proposed that disruption of the TAF II 250 interaction with factors bound to a promoter-upstream CREB/ATF site upstream of the promoter (89) explains the CycA expression defect at the restrictive temperature. Because Tax additively repressed expression from the cyclin A promoter in ts13 cells at 39°C, and because Tax is known to bind CREB/ATF directly (22,77,83), we reasoned that physical sequestration by Tax might explain transcriptional repression. To correlate repression with Tax and CREB/ ATF interaction, we transfected ts13 cells with a Tax H52Q point mutation protein (TaxH52Q) (22) which is defective in binding to CREB.…”

Section: Tax Represses the Cyclin A Promoter In Ts13 And Jurkat Cellsmentioning

confidence: 99%

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CREB/ATF-Dependent Repression of Cyclin A by Human T-Cell Leukemia Virus Type 1 Tax Protein

Kibler

Jeang

2001

J Virol

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Expression of the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax is correlated with cellular transformation contributing to the development of adult T-cell leukemia. Tax has been shown to modulate the activities of several cellular promoters. Existing evidence suggests that Tax need not directly bind to DNA to accomplish these effects but rather that it can act through binding to cellular factors, including members of the CREB/ATF family. Exact mechanisms of HTLV-1 transformation of cells have yet to be fully defined, but the process is likely to include both activation of cellular-growth-promoting factors and repression of cellular tumor-suppressing functions. While transcriptional activation has been well studied, transcriptional repression by Tax, reported recently from several studies, remains less well understood. Here, we show that Tax represses the TATA-less cyclin A promoter. Repression of the cyclin A promoter was seen in both ts13 adherent cells and Jurkat T lymphocytes. Two other TATA-less promoters, cyclin D3 and DNA polymerase ␣, were also found to be repressed by Tax. Interestingly, all three promoters share a common feature of at least one conserved upstream CREB/ATF binding site. In electrophoretic mobility shift assays, we observed that Tax altered the formation of a complex(es) at the cyclin A promoter-derived ATF site. Functionally, we correlated removal of the CREB/ATF site from the promoter with loss of repression by Tax. Furthermore, since a Tax mutant protein which binds CREB repressed the cyclin A promoter while another mutant protein which does not bind CREB did not, we propose that this Tax repression occurs through protein-protein contact with CREB/ATF.Infection with human T-cell leukemia virus type 1 (HTLV-1) has been linked to the development of several diseases: adult T-cell leukemia (ATL), tropical spastic paraparesis, and various neurological disorders termed HTLV-1-associated myelopathy (33). The HTLV-1-encoded oncoprotein Tax has been implicated in the transformation of T cells (reviewed in reference 91), as well as in tumor formation in transgenic mice (26). Although the precise mechanisms utilized by Tax to induce transformation are not known, this protein has been shown to modulate cellular genes that are involved in cellular proliferation and cell cycle control (reviewed in reference 55). Tax up-regulates expression of interleukin-2 (IL-2), IL-2 receptor, c-fos, c-Jun, erg-1, and granulocyte-macrophage colony-stimulating factor (reviewed in references 32 and 51; 52) and represses expression of the ␤-polymerase, c-myb, Lck, and p53 promoters (11,39,48,57,84). Tax has also been shown to affect the functions of IKK␥ (10, 27, 40), c-myc (69), Bax (8), MAD1 (41), cyclin D (56), and MyoD (63).Cyclins are critical factors in cell cycle progression (25,71,72). Cyclins associate with cyclin-dependent kinases and regulate the functions of cellular proteins that are required for progression through the cell cycle (G 1 , S, G 2 , and M) phases. The D cyclins are induced by ...

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Section: Vol 75 2001mentioning

confidence: 99%

Section: Tax Represses the Cyclin A Promoter In Ts13 And Jurkat Cellsmentioning

confidence: 99%

CREB/ATF-Dependent Repression of Cyclin A by Human T-Cell Leukemia Virus Type 1 Tax Protein

Kibler

Jeang

2001

J Virol

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“…Oncogenic effects of Tax may be due to its interaction with cellular proteins, consisting of several transcription factors including CREB, NF-B and SRF, [170][171][172][173] and the family of I B transcriptional inhibitors. 174 I B family proteins contain 6-8 ankyrin motifs.…”

Section: Role Of Ink4 Family In Atllmentioning

confidence: 99%

Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL)

Hatta

Koeffler

2002

Leukemia

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“…Tax 1 is not a direct DNAbinding protein but modulates the expression of cellular and viral genes by interacting with transcription factors involved in several signalling pathways. Specifically, Tax enhances transcription of the viral genome from the long terminal repeat (LTR) by interacting with cyclic AMP response element-binding protein/activating transcription factor (CREB/ATF) and p300/CBP-associated factor (PCAF), which increases their affinity for cAMP responsive elements (CRE) within the LTR (Zhao and Giam, 1991;Suzuki et al, 1993;Jiang et al, 2000). Activation of the nuclear factor (NF)-kB pathway by Tax 1 has a critical role in events leading to ATL development (Sun and Yamaoka, 2005;Matsuoka and Jeang, 2007).…”

Section: Introductionmentioning

confidence: 99%

Functional interaction of HTLV-1 Tax protein with the POZ domain of the transcriptional repressor BCL6

et al. 2009

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The Tax protein encoded by human T-cell leukaemia virus type 1 (HTLV-1) has a pivotal role in T-cell transformation by deregulating cellular signalling pathways. Using the yeast two-hybrid system to screen a human leukocyte cDNA library, we identified BCL6 (B-cell lymphoma 6) as a cellular protein, which interacts with Tax 1. The BCL6 gene encodes a sequence-specific transcriptional repressor that contains a conserved N-terminal poxvirus and zinc finger (POZ) repressor domain and a C-terminal Kruppel-like zinc finger DNA binding domain. Using both in vivo and in vitro methods, we demonstrate that the POZ domain of BCL6 is sufficient for its interaction with Tax 1. Using functional assays, we demonstrate that Tax 1 enhanced the repressive activity of BCL6 and increased the levels of apoptosis induced by BCL6 in osteosarcoma cells indicating that both proteins cooperate in vivo to cause a physiological affect. Furthermore, BCL6 recruited Tax 1 into punctate nuclear structures, which suggests that Tax 1 colocalizes with BCL6 in repressor complexes in vivo. BCL6 expression significantly downregulated both basal and Tax-induced nuclear factor-jB and long terminal repeat activation. This suggests that the expression of BCL6 in HTLV infected cells may contribute to the silencing of viral gene expression and to the long clinical latency associated with HTLV infection.

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The trans-activator tax of human T-cell leukemia virus type 1 (HTLV-1) interacts with cAMP-responsive element (CRE) binding and CRE modulator proteins that bind to the 21-base-pair enhancer of HTLV-1.

Cited by 251 publications

References 38 publications

CREB/ATF-Dependent Repression of Cyclin A by Human T-Cell Leukemia Virus Type 1 Tax Protein

CREB/ATF-Dependent Repression of Cyclin A by Human T-Cell Leukemia Virus Type 1 Tax Protein

Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL)

Functional interaction of HTLV-1 Tax protein with the POZ domain of the transcriptional repressor BCL6

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