Document 0460
 DOCN  M9460460
 TI    Camptothecin inhibits Tat-mediated transactivation of type 1 human
       immunodeficiency virus.
 DT    9404
 AU    Li CJ; Wang C; Pardee AB; Dana-Farber Cancer Institute, Department of
       Biological Chemistry; and Molecular Pharmacology, Harvard Medical
       School, Boston,; Massachusetts 02115.
 SO    J Biol Chem. 1994 Mar 11;269(10):7051-4. Unique Identifier : AIDSLINE
       MED/94171704
 AB    Transcription of type 1 human immunodeficiency virus (HIV-1) is governed
       by the viral long terminal repeat (LTR). By using HIV-1 LTR-directed
       reporter gene systems, we found that the DNA topoisomerase I inhibitor
       camptothecin inhibits Tat-mediated transactivation of HIV-1 LTR. The
       293.27.2 cells that carry a stably transfected HIV-1 LTR-directed lacZ
       gene expression vector (pNAZ) were used. Inhibitions of LTR were
       observed at camptothecin concentrations (IC50 about 0.03 microM, which
       was an order of magnitude lower than for Ro 24-7429), which had minor
       effects on cell survival, expression of the cellular gene gro, or Rous
       sarcoma virus-directed chloramphenicol acetyltransferase (CAT) gene
       expression. Inhibition was also seen with RPMI 8402, which is a human
       CD4-positive lymphocyte line transiently transfected with a HIV-1
       LTR-directed (CAT) gene. Experiments with HIV-1 LTR mutants suggest that
       transactivation response sequence but not NF-kappa B is responsible for
       the inhibition by camptothecin. The target for camptothecin may be a
       cellular factor that is important for the activation of HIV-1 LTR by Tat
       and thus may offer a potential target for therapy of HIV-1 infection.
 DE    Base Sequence  Benzodiazepines/PHARMACOLOGY  Camptothecin/*PHARMACOLOGY
       Cell Line  Gene Expression Regulation, Viral  Gene Products,
       tat/*ANTAGONISTS & INHIB/PHYSIOLOGY  Human  HIV Long Terminal
       Repeat/GENETICS  HIV-1/*DRUG EFFECTS/GENETICS  Molecular Sequence Data
       NF-kappa B/METABOLISM  Oligodeoxyribonucleotides  Regulatory Sequences,
       Nucleic Acid  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Trans-Activation (Genetics)/*DRUG EFFECTS  JOURNAL ARTICLE

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