Abstract:
:Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of the aggressive and fatal disease adult T-cell leukemia. Previous studies have demonstrated that the HTLV-1-encoded Tax protein inhibits the function of tumor suppressor p53 through a Tax-induced NF-kappaB pathway. Given these attributes, we were interested in the activity of small-molecule inhibitor 9-aminoacridine (9AA), an anticancer drug that targets two important stress response pathways, NF-kappaB and p53. In the present study, we have examined the effects of 9AA on HTLV-1-transformed cells. Treatment of HTLV-1-transformed cells with 9AA resulted in a dramatic decrease in cell viability. Consistent with these results, we observed an increase in the percentage of cells in sub-G(1) and an increase in the number of cells positive by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay following treatment of HTLV-1-transformed cells with 9AA. In each assay, HTLV-1-transformed cells C8166, Hut102, and MT2 were more sensitive to treatment with 9AA than control CEM and peripheral blood mononuclear cells. Analyzing p53 function, we demonstrate that treatment of HTLV-1-transformed cells with 9AA resulted in an increase in p53 protein and activation of p53 transcription activity. Of significance, 9AA-induced cell death could be blocked by introduction of a p53 small interfering RNA, linking p53 activity and cell death. These results suggest that Tax-repressed p53 function in HTLV-1-transformed cells is "druggable" and can be restored by treatment with 9AA. The fact that 9AA induces p53 and inhibits NF-kappaB suggests a promising strategy for the treatment of HTLV-1-transformed cells.
journal_name
J Viroljournal_title
Journal of virologyauthors
Jung KJ,Dasgupta A,Huang K,Jeong SJ,Pise-Masison C,Gurova KV,Brady JNdoi
10.1128/JVI.00690-08subject
Has Abstractpub_date
2008-09-01 00:00:00pages
8537-47issue
17eissn
0022-538Xissn
1098-5514pii
JVI.00690-08journal_volume
82pub_type
杂志文章abstract::An in vitro poliovirus RNA-synthesizing system derived from a crude membrane fraction of infected HeLa cells was used to analyze the mechanism of initiation of poliovirus plus-strand RNA synthesis. This system contains an activity that synthesizes the nucleotidyl proteins VPg-pU and VPg-pUpU. These molecules represent...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.1.43-53.1986
更新日期:1986-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.12.4797-4800.1988
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pub_type: 杂志文章
doi:10.1128/JVI.62.1.120-126.1988
更新日期:1988-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01374-15
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01708-19
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.6.2785-2789.1989
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pub_type: 杂志文章
doi:10.1128/JVI.02163-18
更新日期:2019-04-17 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.5690-5697.1994
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abstract::A series of plasmids containing hepatitis A virus (HAV) cDNA was constructed such that positive-strand HAV RNA could be transcribed with T7 RNA polymerase. The plasmids differed in the number of 5'-terminal nucleotides representing the junctions between vectors and HAV sequences that were present in the transcripts. W...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.5.2757-2760.1991
更新日期:1991-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00089-16
更新日期:2016-03-28 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.17.3.841-853.1976
更新日期:1976-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.00722-16
更新日期:2016-06-24 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.42.2.365-371.1982
更新日期:1982-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.7.5051-5059.1997
更新日期:1997-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.10.3914-3917.1988
更新日期:1988-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00820-18
更新日期:2018-09-12 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00896-12
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.14.7653-7666.2004
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.7.3928-3931.1991
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pub_type: 杂志文章
doi:10.1128/jvi.76.21.10685-10691.2002
更新日期:2002-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2014-06-01 00:00:00
abstract::In the spherical capsid of hepatitis B virus (HBV), intermolecular disulfide bonds cross-link the approximately 180 p21.5 capsid protein subunits into a stable lattice. In this study, we used mutant capsid proteins to investigate the role that disulfide bonds and the four p21.5 Cys residues (positions 48, 61, 107, and...
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pub_type: 杂志文章
doi:10.1128/JVI.66.9.5393-5398.1992
更新日期:1992-09-01 00:00:00
abstract::The VP24 protein plays an essential, albeit poorly understood role in the filovirus life cycle. VP24 is only 30% identical between Marburg virus and the ebolaviruses. Furthermore, VP24 from the ebolaviruses is immunosuppressive, while that of Marburg virus is not. The crystal structure of Marburg virus VP24, presented...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03565-13
更新日期:2014-05-01 00:00:00
abstract::To determine the extent and structure of genetic variation in dengue viruses (DENV) on a restricted spatial and temporal scale, we sequenced the E (envelope) genes of DENV-1, -2, and -3 isolates collected in 2001 from children enrolled in a prospective school-based study in Kamphaeng Phet, Thailand, and diagnosed with...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02728-07
更新日期:2008-06-01 00:00:00
abstract::Varicella-zoster virus (VZV) is the causative agent of chickenpox and herpes zoster (shingles). After the primary infection, the virus remains latent in sensory ganglia and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00128-12
更新日期:2012-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2015-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01251-17
更新日期:2018-01-02 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2018-05-29 00:00:00
abstract::Passive transfer of neutralizing antibodies is effective in protecting rhesus macaques against simian/human immunodeficiency virus (SHIV) challenge. In addition to neutralization, effector functions of the crystallizable fragment (Fc) of antibodies are involved in antibody-mediated protection against a number of virus...
journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2011-10-01 00:00:00