       Document 0111
 DOCN  M9460111
 TI    Effects of provirus integration in the Tpl-1/Ets-1 locus in Moloney
       murine leukemia virus-induced rat T-cell lymphomas: levels of
       expression, polyadenylation, transcriptional initiation, and
       differential splicing of the Ets-1 mRNA.
 DT    9404
 AU    Bellacosa A; Datta K; Bear SE; Patriotis C; Lazo PA; Copeland NG;
       Jenkins NA; Tsichlis PN; Fox Chase Cancer Center, Philadelphia,
       Pennsylvania 19111.
 SO    J Virol. 1994 Apr;68(4):2320-30. Unique Identifier : AIDSLINE
       GENBANK/L21901
 AB    The Tpl-1 locus was defined as a genomic DNA region which is targeted by
       provirus insertion during progression of Moloney murine leukemia
       virus-induced rat T-cell lymphomas. Using a panel of 156 (Mus musculus x
       Mus spretus) x Mus musculus interspecific backcross mice, we mapped
       Tpl-1 to mouse chromosome 9 at a distance of 1.2 +/- 0.9 centimorgans
       from the Ets-1 proto-oncogene (S.E. Bear, A. Bellacosa, P.A. Lazo, N.A.
       Jenkins, N.G. Copeland, C. Hanson, G. Levan, and P.N. Tsichlis, Proc.
       Natl. Acad. Sci. USA 86:7495-7499, 1989). In this report, we present
       evidence that all the known Tpl-1 provirus insertions occurred
       immediately 5' of the first exon of Ets-1 (exon A) and that the earlier
       detected distance between Tpl-1 and Ets-1 was due to the high frequency
       of meiotic recombination in the region between the site of provirus
       integration and exon III. Northern (RNA) blot analysis of polyadenylated
       RNA from normal adult rat tissues and Moloney murine leukemia
       virus-induced T-cell lymphomas and hybridization to a Tpl-1/Ets-1 probe
       derived from the 5' end of the gene revealed two lymphoid cell-specific
       RNA transcripts, of 5.5 and 2.2 kb. Sequence analysis of a
       near-full-length (4,991-bp) cDNA clone of the 5.5-kb RNA revealed a
       441-amino-acid open reading frame encoding a protein identical to the
       human and mouse Ets-1 proteins with the exception of five and nine
       species-specific conservative amino acid differences, respectively. The
       steady-state level of the Tpl-1/Ets-1 RNA and of the Ets-1 protein was
       modestly elevated in tumors carrying a provirus in the Tpl-1 locus. The
       relative ratio of the two Ets-1 transcripts, which were shown to arise
       by differential polyadenylation, was not affected by provirus insertion.
       Moreover, the major site of transcriptional initiation, which was
       localized by primer extension 250 bp upstream of the 5' end of the Ets-1
       cDNA clone, was shown to be identical in normal cells and tumors
       carrying a provirus in the Tpl-1 locus. Finally, the differential
       splicing of Ets-1 exon VII was shown by RNase protection to occur at a
       rate of 15 to 26% and to remain unaffected by provirus insertion. The
       subtlety of these effects, in contrast to the strong growth selection of
       cells with a provirus in the Tpl-1/Ets-1 locus, suggests that provirus
       insertion may affect the fine regulation of the gene, perhaps during
       cell cycle progression.
 DE    Alternative Splicing  Amino Acid Sequence  Animal  Base Sequence
       Cloning, Molecular  DNA, Complementary/GENETICS  Lymphoma,
       T-Cell/*MICROBIOLOGY  Molecular Sequence Data  Moloney Leukemia
       Virus/*GENETICS  Polymerase Chain Reaction  Promoter Regions
       (Genetics)/GENETICS  Proto-Oncogene Proteins/*GENETICS  Rats  Rats,
       Inbred F344  Restriction Mapping  *RNA Processing, Post-Transcriptional
       RNA, Messenger/BIOSYNTHESIS/GENETICS  Sequence Analysis, DNA  Sequence
       Homology, Amino Acid  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  Virus Integration/*GENETICS  JOURNAL ARTICLE

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

