送交者: PW 于 2005-11-23, 10:20:18:
Title: Coordinate effects of human immunodeficiency virus type 1 protein Tat and cellular protein Pur alpha on DNA replication initiated at the JC virus origin
Author(s): Daniel DC, Wortman MJ, Schiller RJ, Liu H, Gan L, Mellen JS, Chang CF, Gallia GL, Rappaport J, Khalili K, Johnson EM
Source: JOURNAL OF GENERAL VIROLOGY 82: 1543-1553 Part 7, JUL 2001
Document Type: Article
Language: English
Cited References: 66 Times Cited: 13
Abstract: JC virus (JCV) causes progressive multifocal leukoencephalopathy, a demyelinating disease in brains of individuals with AIDS. Previous work has shown that the Tat protein, encoded by human immunodeficiency virus type 1 (HIV-1), can interact with cellular protein Pur alpha to enhance bath TAR-dependent HIV-1 transcription and JCV late gene transcription. Tat has been shown to activate JCV transcription through interaction with Pur alpha, which binds to promoter sequence elements near the JCV origin of replication. DNA footprinting has shown that Pur alpha and large T-antigen cooperatively interact at several binding sites in the origin and transcriptional control region. Overexpression of Pur alpha inhibits replication initiated at the JCV origin by T-antigen. In transfected glial cells Tat reversed this inhibition and enhanced DNA replication. In an in vitro replication system maximal activation by Tat, more than sixfold the levels achieved with T-antigen alone, was achieved in the presence of Pur alpha, Effects of mutant Tat proteins on both activation of replication and binding to Pur alpha have revealed that Cys22 exerts a conformational effect that affects both activities. The origin of an archetypal strain of JCV was less susceptible to activation of replication by Tat relative to the rearranged Mad-1 strain. These results have revealed a previously undocumented role for Tat in DNA replication and have indicated a regulatory role for JCV origin auxiliary sequences in replication and activation by Tat.
KeyWords Plus: SINGLE-STRANDED-DNA; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CENTRAL-NERVOUS-SYSTEM; HUMAN GLIAL-CELLS; BINDING-PROTEIN; HIV-1 TAT; IN-VITRO; RETINOBLASTOMA PROTEIN; CONTROL ELEMENT; HIGH-AFFINITY
Addresses: Johnson EM (reprint author), Mt Sinai Sch Med, Dept Pathol, Box 1194, New York, NY 10029 USA
Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA
Mt Sinai Sch Med, Dept Mol Biol & Biochem, New York, NY 10029 USA
Mt Sinai Sch Med, DH Ruttenberg Canc Ctr, New York, NY 10029 USA
Temple Univ, Ctr Neurovirol & Canc Biol, Philadelphia, PA 19122 USA
Publisher: SOC GENERAL MICROBIOLOGY, MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND
Subject Category: BIOTECHNOLOGY & APPLIED MICROBIOLOGY; VIROLOGY
IDS Number: 445AU
ISSN: 0022-1317