       Document 0942
 DOCN  M9620942
 TI    The human immunodeficiency virus type-1 Tat protein upregulates Bcl-2
       gene expression in Jurkat T-cell lines and primary peripheral blood
       mononuclear cells.
 DT    9602
 AU    Zauli G; Gibellini D; Caputo A; Bassini A; Negrini M; Monne M; Mazzoni
       M; Capitani S; Institute of Human Anatomy, University of Ferrara, Italy.
 SO    Blood. 1995 Nov 15;86(10):3823-34. Unique Identifier : AIDSLINE
       MED/96068748
 AB    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.
 DE    Apoptosis  Comparative Study  CD4-Positive T-Lymphocytes/*DRUG
       EFFECTS/METABOLISM  DNA, Antisense/GENETICS  DNA, Complementary/GENETICS
       Gene Expression Regulation/*DRUG EFFECTS  Gene Expression Regulation,
       Leukemic/DRUG EFFECTS  Gene Products, tat/GENETICS/*PHYSIOLOGY  Human
       HIV-1/GENETICS/*PHYSIOLOGY  Leukocytes, Mononuclear/*DRUG
       EFFECTS/METABOLISM  Point Mutation  Proto-Oncogene
       Proteins/*BIOSYNTHESIS/GENETICS  Recombinant Fusion
       Proteins/BIOSYNTHESIS  RNA, Messenger/BIOSYNTHESIS  RNA,
       Neoplasm/BIOSYNTHESIS  Support, Non-U.S. Gov't  Trans-Activation
       (Genetics)  Transfection  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

