The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression

Ego, Takeshi; Ariumi, Yasuo; Shimotohno, Kunitada

doi:10.1038/sj.onc.1205701

Cited by 73 publications

(67 citation statements)

References 30 publications

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“…32 Recently, it has been shown that human T-cell leukemia virus type 1 (HTLV-1) Tax protein, which activates transcription from its long terminal repeat by interacting with p300/CBP and CREB, can negatively regulate the gene expression by binding with HDAC1. 33 These cases have a similarity with the relationship of SYT and mSin3A shown in the present study. The mSin3A/HDAC complex might negatively regulate the transcriptional activation mediated by SYT which is associated with transcriptional coactivators such as p300.…”

Section: Discussionsupporting

confidence: 62%

SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with mSin3A, a component of histone deacetylase complex

Itö

Ouchida

Ito

et al. 2004

Laboratory Investigation

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Synovial sarcomas are soft-tissue tumors predominantly affecting children and young adults. They are molecular-genetically characterized by the SYT-SSX fusion gene generated from chromosomal translocation t(X; 18) (p11.2; q11.2). When we screened new gene products that interact with SYT or SSX proteins by yeast two-hybrid assay, we found that mSin3A, a component of the histone deacetylase complex, interacts with SYT but not with SSX. These results were confirmed by mammalian two-hybrid and pull-down assays. Analyses with sequential truncated proteins revealed a main mSin3A-interaction region on the SYT amino-terminal 93 amino acids, and another one on the region between 187th amino acid and break point. In luciferase assay, mSin3A repressed the transcriptional activity of reporter promoter mediated by SYT and hBRM/BRG1. Our results suggest that the histone deacetylase complex containing mSin3A may regulate the transcriptional activation mediated by SYT.

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Section: Discussionsupporting

confidence: 62%

SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with mSin3A, a component of histone deacetylase complex

Itö

Ouchida

Ito

et al. 2004

Laboratory Investigation

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“…Efficient transcription of the HTLV-I promoter requires the formation of a transactivation complex containing Tax HTLV-I , CREB, and CBP/p300 (55). (72). Functionally, these two latter reports have shown the downregulation by HDACs of basal and Tax HTLV-I -activated HTLV-I transcription.…”

Section: Discussionmentioning

confidence: 96%

Deacetylase Inhibitors and the Viral Transactivator TaxBLV Synergistically Activate Bovine Leukemia Virus Gene Expression via a cAMP-responsive Element- and cAMP-responsive Element-binding Protein-dependent Mechanism

Nguyên

Calomme

Wijmeersch

et al. 2004

Journal of Biological Chemistry

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Efficient bovine leukemia virus (BLV) transcription requires the virus-encoded transactivatorBovine leukemia virus (BLV) 1 is a B-lymphotropic retrovirus associated with enzootic bovine leukosis, a disease characterized by an increased number of B-lymphocytes and, in some cases, after a long latency period, by the subsequent development of B-cell leukemia or lymphosarcoma (1). BLV is closely related structurally and biologically to the human T-lymphotropic viruses HTLV-I and HTLV-II (1). Expression of BLV is regulated at the transcriptional level by the virus-encoded transactivator Tax BLV (2, 3). The molecular mechanism by which Tax BLV activates viral transcription is not fully understood. Transactivation by Tax BLV requires three 21-bp imperfect repeats located in the U3 region of the 5Ј long terminal repeat (LTR) (2, 4). These Tax BLV -responsive elements (called TxREs) contain a core octanucleotide sequence with similarity to the cAMP-responsive element (CRE) consensus (TGACGTCA) (5). The BLV CRE-like motifs located in the middle of each TxRE have been shown to serve as binding sites for three members of the basic leucine zipper (bZIP) family of cellular transcription factors: the CRE-binding protein (CREB) and the activating transcription factors-1 and Ϫ2 (ATF-1 and ATF-2) (4, 6). Because there is no evidence for direct binding of Tax BLV to DNA, it has been proposed that Tax BLV transactivation of the BLV promoter could be mediated, as reported for the HTLV-I system, through protein-protein interactions with CREB/ATF (4, 6, 7). The formation of this promoter-bound Tax BLV -CREB/ATF complex could then serve for the recruitment of the multifunctional cellular coactivators CBP (CREB-binding protein) and p300.There is now strong evidence that both transcriptional activation and silencing are mediated through the recruitment of enzymes that control protein acetylation: the histone deacetylases (HDACs) and the histone acetyltransferases (HATs). Acetylation of specific lysine residues within the amino-terminal tails of nucleosomal histones is generally linked to chroma-

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“…This mechanism is indeed rational given the opposing activities of deacetylase and acetylase, that is, that they not only counter-regulate each other catalytically but also non-catalytically (interaction). Although a recent study suggested competition between CREBbinding protein and HDAC1 for binding to a transcription factor using the lysate of cells overexpressing HDAC1 (30), this is the first description of direct competition for binding on a specific interaction region by deacetylase and acetylase.…”

Section: Insight Into Mechanism Of Negative Regulatory Effect Onmentioning

confidence: 99%

“…1F). This amino-terminal region also includes the binding site for Tax (30) and thus may be a common protein-protein interaction surface. Collectively, KLF5-DBD binds to the amino-terminal region of HDAC1.…”

Section: Klf5 and Hdac1 Can Interact In The Cell And Directlymentioning

confidence: 99%

The Deacetylase HDAC1 Negatively Regulates the Cardiovascular Transcription Factor Krüppel-like Factor 5 through Direct Interaction

Matsumura

Suzuki

Aizawa

et al. 2005

Journal of Biological Chemistry

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Transcription is regulated by a network of transcription factors and related cofactors that act in concert with the general transcription machinery. Elucidating their underlying interactions is important for understanding the mechanisms regulating transcription. Recently, we have shown that Krü ppel-like factor KLF5, a member of the Sp/KLF family of zinc finger factors and a key regulator of cardiovascular remodeling, is regulated positively by the acetylase p300 and negatively by the oncogenic regulator SET through coupled interaction and regulation of acetylation. Here, we have shown that the deacetylase HDAC1 can negatively regulate KLF5 through direct interaction. KLF5 interacts with HDAC1 in the cell and in vitro. Gel shift DNA binding assay showed that their interaction inhibits the DNA binding activity of KLF5, suggesting a property of HDAC1 to directly affect the DNA binding affinity of a transcription factor. Reporter assay also revealed that HDAC1 suppresses KLF5-dependent promoter activation. Additionally, overexpression of HDAC1 suppressed KLF5-dependent activation of its endogenous downstream gene, platelet-derived growth factor-A chain gene, when activated by phorbol ester. Further, HDAC1 binds to the first zinc finger of KLF5, which is the same region where p300 interacts with KLF5 and, intriguingly, HDAC1 inhibits binding of p300 to KLF5. Direct competitive interaction between acetylase and deacetylase has been hitherto unknown. Collectively, the transcription factor KLF5 is negatively regulated by the deacetylase HDAC1 through direct effects on its activities (DNA binding activity, promoter activation) and further through inhibition of interaction with p300. These findings suggest a novel role and mechanism for regulation of transcription by deacetylase.Transcription is regulated by a network of regulatory transcription factors and coregulatory proteins (cofactors) that collectively act in concert with the general transcription machinery (1-5). Cofactors, as coactivators or corepressors, exert their activities in main through protein-protein interaction and/or chemical modification (e.g. phosphorylation, acetylation), thus allowing for noncatalytic and/or catalytic regulatory processes. Understanding the molecular mechanisms underlying transcriptional regulation, especially with a focus on protein-protein interaction with coupled chemical modification, is a recent topic of interest.Acetylation is a chemical modification that is linked to transcription and is regulated in main by the catalytic enzymes, acetylase and deacetylase. Recent research has identified the factors bearing acetylase activity (e.g. p300, p300/ CREB-binding protein-associated factor) as well as deacetylase activity (HDACs) and their catalytic roles in transcriptional regulation (6 -10). We have, however, shown that the acetylase p300 not only regulates a DNA binding transcription factor, Sp1, by catalytic means (acetylation) but also that its effects are importantly, as well as unexpectedly, mediated by direct noncatalytic ef...

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The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression

Cited by 73 publications

References 30 publications

SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with mSin3A, a component of histone deacetylase complex

SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with mSin3A, a component of histone deacetylase complex

Deacetylase Inhibitors and the Viral Transactivator TaxBLV Synergistically Activate Bovine Leukemia Virus Gene Expression via a cAMP-responsive Element- and cAMP-responsive Element-binding Protein-dependent Mechanism

The Deacetylase HDAC1 Negatively Regulates the Cardiovascular Transcription Factor Krüppel-like Factor 5 through Direct Interaction

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