Document 0486
 DOCN  M9480486
 TI    Transcriptional suppression of the human T-cell leukemia virus type I
       long terminal repeat occurs by an unconventional interaction of a CREB
       factor with the R region.
 DT    9410
 AU    Xu X; Brown DA; Kitajima I; Bilakovics J; Fey LW; Nerenberg MI;
       Department of Neuropharmacology, Scripps Research Institute, La; Jolla,
       California 92037.
 SO    Mol Cell Biol. 1994 Aug;14(8):5371-83. Unique Identifier : AIDSLINE
       MED/94309657
 AB    To analyze regulation of the human T-cell leukemia virus type I (HTLV-I)
       long terminal repeat (LTR), cell lines were generated from LTR-tax x
       LTR-beta-galactosidase (beta-Gal) doubly transgenic mouse fibroblastic
       tumors. The HTLV-I LTR directs expression of both the tax and lacZ
       genes, and Tax up-modulates both promoters in primary cells. However,
       once cells were transformed by tax, beta-Gal but not tax expression was
       suppressed. Supertransformation of these cells with v-src suppressed
       both beta-Gal and tax expression. This suppression was reversed by
       treatment with the tyrosine kinase inhibitor herbimycin A or protein
       kinase A inhibitor H8. Electrophoretic mobility shift assays
       demonstrated augmented binding in the R but not U3 region. This binding
       was competitively inhibited by a high-affinity CREB oligodeoxynucleotide
       and super-shifted with a specific CREB antibody. Treatment of cells with
       the cyclic AMP analog dibutyryl cyclic AMP also transiently increased
       the R region binding dramatically. In vitro DNase I footprint analysis
       identified a protein-binding sequence in the R region which corresponded
       with suppression. However, this target sequence lacked a conventional
       CREB-binding site. A 70.5-kDa DNA-binding protein was partially purified
       by affinity chromatography, along with a 49-kDa protein which reacted
       with CREB-specific sera. These data demonstrate that HTLV-I LTR
       suppression is associated with CREB factor binding in the R region,
       probably by direct interaction with a 70.5-kDa protein, and provide a
       novel mechanism for maintenance of viral latency.
 DE    Animal  Base Sequence  Binding Sites  Cyclic AMP-Dependent Protein
       Kinases/METABOLISM  DNA-Binding Protein, Cyclic
       AMP-Responsive/*METABOLISM  DNA-Binding Proteins/METABOLISM  *Gene
       Expression Regulation, Viral  Genes, pX  Genes, src  HTLV-I/*GENETICS
       Mice  Mice, Transgenic  Molecular Sequence Data  Nuclear
       Proteins/METABOLISM  *Repetitive Sequences, Nucleic Acid  RNA,
       Messenger/GENETICS  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Transcription, Genetic  JOURNAL ARTICLE

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