Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

Michael, Bindhu; Nair, Amrithraj M.; Hiraragi, Hajime; Shen, Lei; Feuer, Gerold; Boris‐Lawrie, Kathleen; Lairmore, Michael Dale

doi:10.1186/1742-4690-1-39

Cited by 35 publications

(19 citation statements)

References 57 publications

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“…Future studies will further characterize p30 II -Myc/ TIP60 biochemical interactions and determine their roles in cell-cycle deregulation and transformation by HTLV-1. Collectively, these findings suggest that nucleolar p30 II functions as a post-transcriptional regulator of Tax/Rex mRNA (Nicot et al, 2004;Younis et al, 2004) and suggest that, through interactions with transcriptional cofactors such as p300/CBP and TIP60, p30 II may also influence RNA Pol II nucleoplasmic transcription complexes to modulate the expression of viral and cellular genes (Figure 3c) (Zhang et al, 2000Michael et al, 2004).…”

Section: Htlv-1 Orf I: P12 I a Modulator Of T-cell Immune Functionsmentioning

confidence: 99%

“…The Gal4 (DBD)-p30 II fusion protein interacts with p300; likewise, HA-tagged p30 II was shown to coimmunoprecipitate with p300 and disrupt formation of Tax-p300-HTLV-1 21 bp repeat complexes in streptavidin-agarose pulldown experiments . Results of glutathione-S-transferase (GST) pull-down assays demonstrated that in vitro translated p30 II interacts with amino-acid residues 1-595 of GST-p300 and residues 451-682 of GST-CBP, which comprise the kinaseinducible exchange (KIX) domain of CBP that is known to bind to Tax (Kwok et al, 1996;Giebler et al, 1997;Harrod et al, 1998;Zhang et al, 2001;Michael et al, 2004) recently reported Affymetrix microarray gene expression analyses of Jurkat cells stably transduced with a lentiviral vector expressing p30 II . Their results indicate that p30 II represses many cellular genes, particularly adhesion molecules, such as integrins and cadherins, but increases the expression of certain target genes involved in T-cell activation and apoptosis (Michael et al, 2004).…”

Section: Htlv-1 Orf I: P12 I a Modulator Of T-cell Immune Functionsmentioning

confidence: 99%

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Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions

et al. 2005

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The human T-cell leukemia/lymphoma virus (HTLV) genome, in addition to the structural Gag and Env proteins and retroviral enzymes, carries a region at its 3 0 end originally designated pX. To date, we know that this region encodes two essential transcriptional and posttranscriptional positive regulators of viral expression, the Tax and Rex proteins, respectively (reviewed elsewhere in this issue). Here, we will review current knowledge of the functions of three additional proteins encoded in the pX region, p12 I , p13 II , and p30 II .

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Section: Htlv-1 Orf I: P12 I a Modulator Of T-cell Immune Functionsmentioning

confidence: 99%

Section: Htlv-1 Orf I: P12 I a Modulator Of T-cell Immune Functionsmentioning

confidence: 99%

Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions

et al. 2005

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“…Plasmids were transfected using SuperFect (Qiagen, Valencia, CA) according to the manufacturer's instructions. Transduction of 293T and Jurkat T cells with pWPT-IRES-GFP and pWPT-p30-HA-IRES-GFP was performed as described (20). For ectopic expression of p30, 293T cells were transfected with 10 g of pTriEx4-Neo (mock), pTriEx-Neo-S-GFP, or pTriEx4-Neo-S-p30-HA (Novagen, Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

“…We reported that p30 differentially modulates the activity of HTLV-1 promoter-driven reporter genes (18) through its interaction with the transcriptional coactivator p300 (19). In Jurkat T cells, p30 alters the expression of a variety of cellular genes and also enhances signal pathways important for T cell growth and survival (20). Ectopically expressed p30 leads to the retention of tax/rex mRNA in the nucleus (15, 21).…”

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confidence: 99%

Human T-lymphotropic Virus Type 1 p30 Interacts with REGγ and Modulates ATM (Ataxia Telangiectasia Mutated) to Promote Cell Survival

Anupam¹,

Datta²,

Kesic³

et al. 2011

Journal of Biological Chemistry

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Human T-lymphotropic virus type 1 (HTLV-1) is a causative agent of adult T cell leukemia/lymphoma and a variety of inflammatory disorders. HTLV-1 encodes a nuclear localizing protein, p30, that selectively alters viral and cellular gene expression, activates G 2 -M cell cycle checkpoints, and is essential for viral spread. Here, we used immunoprecipitation and affinity pulldown of ectopically expressed p30 coupled with mass spectrometry to identify cellular binding partners of p30. Our data indicate that p30 specifically binds to cellular ATM (ataxia telangiectasia mutated) and REG␥ (a nuclear 20 S proteasome activator). Under conditions of genotoxic stress, p30 expression was associated with reduced levels of ATM and increased cell survival. Knockdown or overexpression of REG␥ paralleled p30 expression, suggesting an unexpected enhancement of p30 expression in the presence of REG␥. Finally, size exclusion chromatography revealed the presence of p30 in a high molecular mass complex along with ATM and REG␥. On the basis of our findings, we propose that HTLV-1 p30 interacts with ATM and REG␥ to increase viral spread by facilitating cell survival. Human T-lymphotropic virus type 1 (HTLV-1)2 is a complex deltaretrovirus and the first reported human retrovirus linked to malignancy (1, 2). It is estimated that ϳ20 million people worldwide are infected with HTLV-1 (3). Approximately five percent of these infected individuals will develop one of a variety of immunopathologic or neoplastic conditions (reviewed in Ref. 4). Two well characterized pathological conditions associated with HTLV-1 infection are adult T cell leukemia/lymphoma, a highly aggressive T cell malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis, an immune-mediated neurodegenerative condition (5, 6). The prolonged latency between acquisition of infection and disease expression indicates a highly regulated host-virus relationship that promotes survival of HTLV-1-infected cell reservoirs.HTLV-1 contains genes that encode typical retroviral structural and enzymatic proteins such as Gag, Pol, and Env, as well as regulatory proteins Tax and Rex (reviewed in Ref. 4). The pX region of HTLV-1 contains open reading frames that also encode for various nonstructural proteins (p12, p13, HBZ, and p30) that are essential to viral transmission and spread (7-12).HTLV-1 p30 is a nuclear and nucleolar localizing protein encoded by a doubly spliced mRNA from ORF II of the pX region of the viral genome (13, 14) that modulates viral and cellular gene expression by transcriptional and post-translational mechanisms (14, 15). HTLV-1-infected individuals produce cytotoxic T cells and antibodies to p30 peptides (16,17). We reported that p30 differentially modulates the activity of HTLV-1 promoter-driven reporter genes (18) through its interaction with the transcriptional coactivator p300 (19). In Jurkat T cells, p30 alters the expression of a variety of cellular genes and also enhances signal pathways important for T cell growth and survival (20). Ectopical...

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“…These proteins are important for in vivo viral infectivity, host cell activation, and regulation of gene transcription (Collins et al, 1998;Ciminale et al, 1999;Trovato et al, 1999;Albrecht et al, 2000Albrecht et al, , 2002Bartoe et al, 2000;D'Agostino et al, 2000;Zhang et al, 2000Zhang et al, , 2001Ding et al, 2002;Franchini et al, 2003;Kim et al, 2003;Michael et al, 2004;Nicot et al, 2004;Younis et al, 2004). The role of these accessory proteins in HTLV-1-mediated transformation has not been …”

Section: Htlv-1 Replication and Mechanisms Of Carcinogenesismentioning

confidence: 99%

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

2005

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Over the past 25 years, animal models of human T-lymphotropic virus type 1 (HTLV-1) infection and transformation have provided critical knowledge about viral and host factors in adult T-cell leukemia/lymphoma (ATL). The virus consistently infects rabbits, some non-human primates, and to a lesser extent rats. In addition to providing fundamental concepts in viral transmission and immune responses against HTLV-1 infection, these models have provided new information about the role of viral proteins in carcinogenesis. Mice and rats, in particular immunodeficient strains, are useful models to assess immunologic parameters mediating tumor outgrowth and therapeutic invention strategies against lymphoma. Genetically altered mice including both transgenic and knockout mice offer important models to test the role of specific viral and host genes in the development of HTLV-1-associated lymphoma. Novel approaches in genetic manipulation of both HTLV-1 and animal models are available to address the complex questions that remain about viral-mediated mechanisms of cell transformation and disease. Current progress in the understanding of the molecular events of HTLV-1 infection and transformation suggests that answers to these questions are approachable using animal models of HTLV-1-associated lymphoma Oncogene (2005) 24, 6005-6015.

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Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

Cited by 35 publications

References 57 publications

Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions

Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions

Human T-lymphotropic Virus Type 1 p30 Interacts with REGγ and Modulates ATM (Ataxia Telangiectasia Mutated) to Promote Cell Survival

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

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