scholarly journals p300-Mediated Tax Transactivation from Recombinant Chromatin: Histone Tail Deletion Mimics Coactivator Function

2002 ◽  
Vol 22 (1) ◽  
pp. 127-137 ◽  
Author(s):  
Sara A. Georges ◽  
W. Lee Kraus ◽  
Karolin Luger ◽  
Jennifer K. Nyborg ◽  
Paul J. Laybourn
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Leukemia Virus ◽  
Acetyl Coa ◽  
Histone Tails ◽  
Cell Leukemia Virus Type ◽  
Cellular Transcription Factor ◽  
Amino Terminal ◽  
Human T Cell

ABSTRACT Efficient transcription of the human T-cell leukemia virus type 1 (HTLV-1) genome requires Tax, a virally encoded oncogenic transcription factor, in complex with the cellular transcription factor CREB and the coactivators p300/CBP. To examine Tax transactivation in vitro, we used a chromatin assembly system that included recombinant core histones. The addition of Tax, CREB, and p300 to the HTLV-1 promoter assembled into chromatin activated transcription several hundredfold. Chromatin templates selectively lacking amino-terminal histone tails demonstrated enhanced transcriptional activation by Tax and CREB, with significantly reduced dependence on p300 and acetyl coenzyme A (acetyl-CoA). Interestingly, Tax/CREB activation from the tailless chromatin templates retained a substantial requirement for acetyl-CoA, indicating a role for acetyl-CoA beyond histone acetylation. These data indicate that during Tax transcriptional activation, the amino-terminal histone tails are the major targets of p300 and that tail deletion and acetylation are functionally equivalent.

scholarly journals Tax Recruitment of CBP/p300, via the KIX Domain, Reveals a Potent Requirement for Acetyltransferase Activity That Is Chromatin Dependent and Histone Tail Independent

2003 ◽  
Vol 23 (10) ◽  
pp. 3392-3404 ◽  
Author(s):  
Sara A. Georges ◽  
Holli A. Giebler ◽  
Philip A. Cole ◽  
Karolin Luger ◽  
Paul J. Laybourn ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Physical Interaction ◽  
Cell Leukemia Virus Type ◽  
Acetyltransferase Activity ◽  
Amino Terminal ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Functional Relevance ◽  
Kix Domain

ABSTRACT Robust transcription of human T-cell leukemia virus type 1 (HTLV-1) genome requires the viral transactivator Tax. Although Tax has been previously shown to interact with the KIX domain of CBP/p300 in vitro, the precise functional relevance of this interaction remains unclear. Using two distinct approaches to interrupt the physical interaction between Tax and KIX, we find that Tax transactivation from chromatin templates is strongly dependent on CBP/p300 recruitment via the KIX domain. Additionally, we find that the primary functional contribution of CBP/p300 to Tax transactivation resides in the intrinsic acetyltransferase activity of the coactivators. These studies unexpectedly uncover a specific requirement for CBP/p300 acetyltransferase activity on chromatin templates assembled with nucleosomes lacking their amino-terminal tails. Together, these data indicate that the KIX domain of CBP/p300 is essential for targeting the acetyltransferase activity of the coactivator to the Tax-CREB (Tax/CREB) complex. Significantly, these observations reveal the presence of one or more CBP/p300 acetyltransferase targets that function specifically on chromatin templates, are independent of the histone tails, and are critical to Tax transactivation.

scholarly journals Human T-Cell Leukemia Virus Type 1 (HTLV-1) bZIP Protein Interacts with the Cellular Transcription Factor CREB To Inhibit HTLV-1 Transcription

2006 ◽  
Vol 81 (4) ◽  
pp. 1543-1553 ◽  
Author(s):  
Isabelle Lemasson ◽  
Matthew R. Lewis ◽  
Nicholas Polakowski ◽  
Patrick Hivin ◽  
Marie-Hélène Cavanagh ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Cell Leukemia Virus Type ◽  
Cellular Transcription Factor ◽  
Human T Cell ◽  
Bzip Domain ◽  
T Cell Leukemia Virus ◽  
Cellular Transcription

ABSTRACT The complex human T-cell leukemia virus type 1 (HTLV-1) retrovirus encodes several proteins that are unique to the virus within its 3′-end region. Among them, the viral transactivator Tax and posttranscriptional regulator Rex are well characterized, and both positively regulate HTLV-1 viral expression. Less is known about the other regulatory proteins encoded in this region of the provirus, including the recently discovered HBZ protein. HBZ has been shown to negatively regulate basal and Tax-dependent HTLV-1 transcription through its ability to interact with specific basic-leucine zipper (bZIP) proteins. In the present study, we found that HBZ reduces HTLV-1 transcription and virion production. We then characterized the interaction between HBZ and the cellular transcription factor CREB. CREB plays a critical role in Tax-mediated HTLV-1 transcription by forming a complex with Tax that binds to viral cyclic AMP-response elements (CREs) located within the viral promoter. We found that HBZ and CREB interact in vivo and directly in vitro, and this interaction occurs through the bZIP domain of each protein. We also found that CREM-Ia and ATF-1, which share significant homology in their bZIP domains with the bZIP domain of CREB, interact with HBZ-bZIP. The interaction between CREB and HBZ prevents CREB binding to the viral CRE elements in vitro and in vivo, suggesting that the reduction in HTLV-1 transcription by HBZ is partly due to the loss of CREB at the promoter. We also found that HBZ displaces CREB from a cellular CRE, suggesting that HBZ may deregulate CREB-dependent cellular gene expression.

scholarly journals Biochemical Characterization, Specificity and Inhibition Studies of HTLV-1, HTLV-2, and HTLV-3 Proteases

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 127
Author(s):  
Norbert Kassay ◽  
János András Mótyán ◽  
Krisztina Matúz ◽  
Mária Golda ◽  
József Tőzsér
Keyword(s):  
T Cell ◽  
Biochemical Characterization ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

The human T-lymphotropic viruses (HTLVs) are causative agents of severe diseases including adult T-cell leukemia. Similar to human immunodeficiency viruses (HIVs), the viral protease (PR) plays a crucial role in the viral life-cycle via the processing of the viral polyproteins. Thus, it is a potential target of anti-retroviral therapies. In this study, we performed in vitro comparative analysis of human T-cell leukemia virus type 1, 2, and 3 (HTLV-1, -2, and -3) proteases. Amino acid preferences of S4 to S1′ subsites were studied by using a series of synthetic oligopeptide substrates representing the natural and modified cleavage site sequences of the proteases. Biochemical characteristics of the different PRs were also determined, including catalytic efficiencies and dependence of activity on pH, temperature, and ionic strength. We investigated the effects of different HIV-1 PR inhibitors (atazanavir, darunavir, DMP-323, indinavir, ritonavir, and saquinavir) on enzyme activities, and inhibitory potentials of IB-268 and IB-269 inhibitors that were previously designed against HTLV-1 PR. Comparative biochemical analysis of HTLV-1, -2, and -3 PRs may help understand the characteristic similarities and differences between these enzymes in order to estimate the potential of the appearance of drug-resistance against specific HTLV-1 PR inhibitors.

scholarly journals Group I p21-activated kinases facilitate Tax-mediated transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats

Retrovirology ◽  
2013 ◽  
Vol 10 (1) ◽  
pp. 47 ◽  
Author(s):  
Ching-Ping Chan ◽  
Yeung-Tung Siu ◽  
Kin-Hang Kok ◽  
Yick-Pang Ching ◽  
Hei-Man Vincent Tang ◽  
...  
Keyword(s):  
T Cell ◽  
Transcriptional Activation ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Long Terminal Repeats ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
Group I ◽  
T Cell Leukemia Virus

scholarly journals Tax and Overlapping Rex Sequences Do Not Confer the Distinct Transformation Tropisms of Human T-Cell Leukemia Virus Types 1 and 2

2003 ◽  
Vol 77 (14) ◽  
pp. 7728-7735 ◽  
Author(s):  
Jianxin Ye ◽  
Li Xie ◽  
Patrick L. Green
Keyword(s):  
T Cells ◽  
T Cell ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are distinct oncogenic retroviruses that infect several cell types but display their biological and pathogenic activity only in T cells. Previous studies have indicated that in vivo HTLV-1 has a preferential tropism for CD4+ T cells, whereas HTLV-2 in vivo tropism is less clear but appears to favor CD8+ T cells. Both CD4+ and CD8+ T cells are susceptible to HTLV-1 and HTLV-2 infection in vitro, and HTLV-1 has a preferential immortalization and transformation tropism of CD4+ T cells, whereas HTLV-2 immortalizes and transforms primarily CD8+ T cells. The molecular mechanism that determines this tropism of HTLV-1 and HTLV-2 has not been determined. HTLV-1 and HTLV-2 carry the tax and rex transregulatory genes in separate but partially overlapping reading frames. Since Tax has been shown to be critical for cellular transformation in vitro and interacts with numerous cellular processes, we hypothesized that the viral determinant of transformation tropism is encoded by tax. Using molecular clones of HTLV-1 (Ach) and HTLV-2 (pH6neo), we constructed recombinants in which tax and overlapping rex genes of the two viruses were exchanged. p19 Gag expression from proviral clones transfected into 293T cells indicated that both recombinants contained functional Tax and Rex but with significantly altered activity compared to the wild-type clones. Stable transfectants expressing recombinant viruses were established, irradiated, and cocultured with peripheral blood mononuclear cells. Both recombinants were competent to transform T lymphocytes with an efficiency similar to that of the parental viruses. Flow cytometry analysis indicated that HTLV-1 and HTLV-1/TR2 had a preferential tropism for CD4+ T cells and that HTLV-2 and HTLV-2/TR1 had a preferential tropism for CD8+ T cells. Our results indicate that tax/rex in different genetic backgrounds display altered functional activity but ultimately do not contribute to the different in vitro transformation tropisms. This first study with recombinants between HTLV-1 and HTLV-2 is the initial step in elucidating the different pathobiologies of HTLV-1 and HTLV-2.

E1A-mediated activation of the adenovirus E4 promoter can occur independently of the cellular transcription factor E4F

1991 ◽  
Vol 11 (9) ◽  
pp. 4297-4305
Author(s):  
C Jones ◽  
K A Lee
Keyword(s):  
Transcription Factor ◽  
Hela Cells ◽  
Transcriptional Activation ◽  
Promoter Activity ◽  
Core Motif ◽  
Cellular Transcription Factor ◽  
The Core ◽  
Cellular Factors

The cellular factors E4F and ATF-2 (a member of the activating transcription factor [ATF] family) bind to common sites in the adenovirus E4 promoter and have both been suggested to mediate transcriptional activation by the viral E1A protein. To assess the role of E4F, we have introduced mutations into the E4F/ATF binding sites of the E4 promoter and monitored promoter activity in HeLa cells. We find that the core motif (TGACG) of the E4F/ATF binding site is important for E4 promoter activity. However, a point mutation adjacent to the core motif that reduces E4F binding (but has no effect on ATF binding) has no effect on E4 promoter activity. Together with previous results, these findings indicate that there are at least two cellular factors (a member of the ATF family and E4F) that can function with E1A to induce transcription of the E4 promoter. We also find that certain mutations strongly reduce E4 transcription in vivo but have no effect on ATF-2 binding in vitro. These results are therefore incompatible with the possibility that (with respect to members of the ATF family) ATF-2 alone can function with E1A to transactivate the E4 promoter in HeLa cells.

scholarly journals In vitro infection of human macrophages with human T-cell leukemia virus type 1

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1598-1606 ◽  
Author(s):  
T de Revel ◽  
A Mabondzo ◽  
G Gras ◽  
B Delord ◽  
P Roques ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human Macrophages ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Abstract The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases.

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