title: Activation of Bcl-2 promoter-directed gene expression by the human immunodeficiency virus type-1 Tat protein.
abstract: Human immunodeficiency virus type 1 (HIV-1) Tat transcriptionally activates expression from a number of viral and cellular promoters. Recent studies demonstrate the ability of Tat to differentially modulate cellular responses to apoptotic signaling. The antiapoptotic effects of Tat appear to correlate with increased expression of Bcl-2, a cellular protein that enhances cellular survival. Here, endogenous expression of HIV-1 Tat in HeLa and Jurkat cells elevates levels of Bcl-2. Transient expression assays performed in HeLa cells demonstrate that Tat directly or indirectly enhances Bcl-2 promoter-directed gene expression by more than 10-fold. Analyses of Tat mutants demonstrate that two noncontiguous regions in the N- and C-termini of Tat mediate maximal transactivation of the Bcl-2 promoter. The requirement for C-terminal sequences contrasts with transactivation of the HIV-1 long terminal repeat in which the N-terminal 57 amino acids are required but downstream residues are not. Bcl-2 promoter analyses suggest that sequences required for Tat responsiveness are located upstream of P1 and between the P1 and P2 promoter units. Results from these studies reveal effects of HIV-1 Tat on Bcl-2 expression and provide a putative mechanism by which endogenously expressed Tat affects cellular survival through the up-regulation of Bcl-2.
mesh_terms: D001665:Binding Sites; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus