       Document 0393
 DOCN  M9620393
 TI    Evidence that a cell cycle regulator, E2F1, down-regulates
       transcriptional activity of the human immunodeficiency virus type 1
       promoter.
 DT    9602
 AU    Kundu M; Srinivasan A; Pomerantz RJ; Khalili K; Department of
       Biochemistry and Molecular Biology, Jefferson; Institute of Molecular
       Medicine, Thomas Jefferson University,; Philadelphia, Pennsylvania
       19107, USA.
 SO    J Virol. 1995 Nov;69(11):6940-6. Unique Identifier : AIDSLINE
       MED/96013795
 AB    Proliferation of eukaryotic cells is orchestrated by a series of
       cellular proteins which participate in various stages of the cell cycle
       to guide the cell through mitosis. Some of these proteins, including
       E2F1, play a critical role in G1 and S phases by coordinately regulating
       expression of several important cell cycle-associated genes. On the
       basis of recent observations indicating a block in human
       immunodeficiency virus type 1 (HIV-1) replication in cells arrested in
       G1/S phase of the cell cycle, we sought to evaluate the regulatory
       action of E2F1 on transcription from the HIV-1 long terminal repeat
       (LTR). Results from transient transfection of cells with an E2F1
       expression plasmid indicated that E2F1 has the ability to suppress basal
       transcriptional activity of the LTR and to diminish the extent of the
       Tat-induced activation of the viral promoter. Deletion analysis of the
       HIV-1 LTR in transfection studies revealed the presence of two major
       elements responsive to E2F1 repression located distally (-454 to 381)
       and proximally (-117 to -80) with respect to the +1 transcription start
       site. E2F1-mediated suppression of LTR activity was observed in a wide
       range of human cell lines. Expression of E2F1 by a transgene showed an
       inhibitory effect on the levels of reverse transcriptase activity
       obtained upon introduction of the proviral genome into cells. The data
       presented in this study suggest that cellular regulatory proteins
       involved in the progression of cells through the mitotic cycle could
       play crucial roles in determining the efficiency of HIV-1 replication
       during the various stages of infection. The possible roles of these
       factors in viral latency and activation are discussed.
 DE    *Cell Cycle  Cell Line  Chloramphenicol Acetyltransferase/BIOSYNTHESIS
       *Gene Expression Regulation, Viral  Gene Products, tat/BIOSYNTHESIS  G1
       Phase  Hela Cells  Human  *HIV Long Terminal Repeat
       HIV-1/*GENETICS/*PHYSIOLOGY  *Promoter Regions (Genetics)  Recombinant
       Fusion Proteins/BIOSYNTHESIS  RNA-Directed DNA Polymerase/BIOSYNTHESIS
       S Phase  Sequence Deletion  Support, U.S. Gov't, P.H.S.
       *Trans-Activation (Genetics)  Transcription Factors/*METABOLISM
       Transfection  Tumor Cells, Cultured  *Virus Replication  JOURNAL ARTICLE

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

