The Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax Inhibits the Transcriptional Activity of c-Myb through Competition for the CREB Binding Protein

Colgin, M.; Nyborg, Jennifer K.

doi:10.1128/jvi.72.11.9396-9399.1998

Cited by 52 publications

(18 citation statements)

References 31 publications

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“…Let-7i, miR-132, miR-199a) of many host cellular miRNAs [67]. The modulation of these host miRNAs has an effect on the expression of cellular proteins such as p300, NF-kB, and BRM, to name a few, which are all recruited by Tax and play a key role in activating HTLV-1 gene transcription [5,[30][31][32][33][34][35][36][38][39][40][44][45]56,60,[68][69][70][71]. To better define the functional significance of Drosha downregulation by Tax, we transfected 293T cells with pACH.Tax (5 mg) and 24 hours later added back pGFP-Drosha (10 mg).…”

Section: Suppression Of Cellular Mirnas By Htlv-1 Can Be Rescued By Omentioning

confidence: 99%

“…This occurs through transcriptional induction of TREs, posttranslational modifications of TRE-binding factors, and binding with transcription factors. Tax is known to interact with the transcription factors CREB, serum-responsive factor (SRF), and NF-kB as well as with the cell cycle related proteins Cyclin D2 and D3, mitotic checkpoint regulators (MAD1), cyclin-dependent kinases (cdks), cdk inhibitors p16 INK4a and p21/waf1, and p53 [5,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. Phosphorylation of Tax is necessary for Tax localization in nuclear bodies as well as activation of cellular gene expression through the NF-kB pathway.…”

Section: Introductionmentioning

confidence: 99%

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Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery

et al. 2012

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The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus.

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Section: Suppression Of Cellular Mirnas By Htlv-1 Can Be Rescued By Omentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery

et al. 2012

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“…Tax protein recruits DNA-binding cellular proteins including ATF/CREB, which associates with the CREB-binding protein (CBP)/p300 (14,15), in complexes that facilitate access to the TREs. Tax protein also directly binds the transcriptional coactivators, CBP/p300 (16)(17)(18)(19)(20) and P/CAF, (21), both proteins containing intrinsic histone acetyltransferase (HAT) activity (22). It has been shown that HAT enzymes lead to histone acetylation and promote transcription in part by relaxing specific nucleosomal-DNA interactions, facilitating the binding of transcription factors to their target gene promoters.…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase 3 represses HTLV-1 tax transcription

et al. 2006

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We examined the epigenetic mechanisms involved in human T-cell lymphotropic virus type 1 (HTLV-1) Tax expression. Blockade of histone deacetylation with trichostatin A (TSA) resulted in Tax upregulation. Using a chromatin immunoprecipitation (ChIP) assay, we verified local histone hyperacetylation at the HTLV-1 LTR in response to TSA. In agreement, HDAC3 transfection led to reductions in both Tax expression and histone acetylation. HDAC3 mutations and deletions spanning the catalytic site had variable ability to repress Tax, but HDAC activity was not essential for repression. Immunoprecipitation studies revealed that Tax co-exists in a complex containing both histone deacetylase 1 (HDAC1) and 3 (HDAC3). Our results suggest that HDACs may actively participate in the repression of HTLV-1 Tax transcription.

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“…p300 mediates the activities of various transcription factors; however, its availability in the cell is limited (Petrij et al, 1995). A variety of cellular proteins are known to compete with each other for binding to p300 (Colgin and Nyborg, 1998). This environment of competition between transcription factors for co-activator binding provides an additional layer of tightly regulated gene expression.…”

Section: Introductionmentioning

confidence: 99%

Calcium-dependent enhancement of transcription of p300 by human T-lymphotropic type 1 p12I

et al. 2006

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Human T-lymphotropic virus type 1 (HTLV-1) p12I localizes to the endoplasmic reticulum and Golgi causing sustained release of calcium, T cell activation, and enhanced expression of several calcium-regulated genes. In recent microarray studies, p300 mRNA was increased in T cells expressing p12I. The co-activator p300 is a key regulator of cellular and viral transcription; however, factors that influence its transcriptional regulation are less well studied. We hypothesized that the transcription of p300 is calcium dependent and that sustained low magnitude increases in intracellular calcium may enhance the transcription of p300. Herein, we report enhanced expression of p300 in T cells by p12I in a calcium-dependent, but calcineurin-independent manner. Sustained low magnitude calcium release induced by ionomycin in T cells was sufficient to increased mRNA and protein levels of p300 resulting in enhanced transcription from a p300-dependent promoter. Promoter analysis of the p300 gene was used to predict calcium-responsive transcription factor binding sites. Using mutant forms of p12I, we demonstrate that ER localization of the viral protein is required to increase p300. In addition, p12I reversed the repression of HTLV-1 LTR-driven transcription by HTLV-1 p30II, a p300-binding protein. HTLV-1 p12I-mediated enhancement of p300 expression represents a novel mechanism of regulation of cellular gene expression by viral proteins. By targeting a ubiquitous second messenger such as calcium, HTLV-1 p12I may regulate the expression of the cellular transcriptional co-activator p300 to modulate viral gene expression and promote lymphocyte survival.

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The Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax Inhibits the Transcriptional Activity of c-Myb through Competition for the CREB Binding Protein

Cited by 52 publications

References 31 publications

Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery

Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery

Histone deacetylase 3 represses HTLV-1 tax transcription

Calcium-dependent enhancement of transcription of p300 by human T-lymphotropic type 1 p12I

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