Linked Life Data

7579350

Source:http://linkedlifedata.com/resource/pubmed/id/7579350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1995-12-19
pubmed:abstractText
The regulatory Tat protein of human immunodeficiency virus type-1 (HIV-1) exerts a pleyotropic activity on the survival and proliferation of different cell types in culture. In this report, we investigated the effect of either endogenous or exogenous Tat on Bcl-2 proto-oncogene expression and cell survival in Jurkat T-cell lines and primary peripheral blood mononuclear cells. Stable and transient transfections of Jurkat cells with the cDNA of tat and a plasmid containing Bcl-2 promoter in front of CAT (Bcl-2 Pr/CAT) stimulated CAT activity and showed an increase of Bcl-2 mRNA and protein expression. This effect was specifically related to tat, because Jurkat cells transfected with the cDNA of tat in antisense orientation, tat carrying a mutation in the amino acid cys22-gly22, or the control vector alone (pRPneo-SL3) did not show any significant difference in Bcl-2 promoter activity with respect to parental Jurkat cells. We also observed a specific correlation between tat-induced Bcl-2 gene expression and inhibition of apoptosis induced by serum withdrawal. Our results suggest that the structural integrity of the activation domain of Tat was required for the promotion of the Bcl-2 promoter and Jurkat cell survival, because a single mutation in the aminoacid cys22 was sufficient to completely block the upregulation of Bcl-2 and inhibition of apoptosis. Moreover, picomolar concentrations of native or recombinant Tat were able to upregulate Bcl-2 expression both in Jurkat and primary peripheral blood mononuclear cells, suggesting that extracellular Tat, actively released by infected cells, may also play a significant role in suppressing apoptosis. An aberrant cell survival of lymphoid cells consequent to the upregulation of Bcl-2 may represent an additional pathogenetic mechanism that could help explain both the dysregulated immune response and the frequent occurrence of hyperplastic/neoplastic disorders in HIV-1-seropositive individuals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3823-34
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7579350-Apoptosis, pubmed-meshheading:7579350-CD4-Positive T-Lymphocytes, pubmed-meshheading:7579350-DNA, Antisense, pubmed-meshheading:7579350-DNA, Complementary, pubmed-meshheading:7579350-Gene Expression Regulation, pubmed-meshheading:7579350-Gene Expression Regulation, Leukemic, pubmed-meshheading:7579350-Gene Products, tat, pubmed-meshheading:7579350-HIV-1, pubmed-meshheading:7579350-Humans, pubmed-meshheading:7579350-Leukocytes, Mononuclear, pubmed-meshheading:7579350-Point Mutation, pubmed-meshheading:7579350-Proto-Oncogene Proteins, pubmed-meshheading:7579350-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:7579350-RNA, Messenger, pubmed-meshheading:7579350-RNA, Neoplasm, pubmed-meshheading:7579350-Recombinant Fusion Proteins, pubmed-meshheading:7579350-Transcriptional Activation, pubmed-meshheading:7579350-Transfection, pubmed-meshheading:7579350-Tumor Cells, Cultured, pubmed-meshheading:7579350-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
1995
pubmed:articleTitle
The human immunodeficiency virus type-1 Tat protein upregulates Bcl-2 gene expression in Jurkat T-cell lines and primary peripheral blood mononuclear cells.
pubmed:affiliation
Institute of Human Anatomy, University of Ferrara, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't