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Titolo:
Suppressor mutations within the core binding factor (CBF/AML1) binding site of a T-cell lymphomagenic retrovirus
Autore:
Martiney, MJ; Levy, LS; Lenz, J;
Indirizzi:
Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 ol Genet, Bronx, NY 10461 USA Tulane Univ, Sch Med, New Orleans, LA 70112 USA Tulane Univ New Orleans LA USA 70112 , Sch Med, New Orleans, LA 70112 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 3, volume: 73, anno: 1999,
pagine: 2143 - 2152
SICI:
0022-538X(199903)73:3<2143:SMWTCB>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
MURINE LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; I TRANSCRIPTIONAL ACTIVATORS; DISEASE SPECIFICITY; ENHANCER SEQUENCES; PROTEIN-BINDING; C-MYC; SL3-3; IDENTIFICATION; ELEMENTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Lenz, J Albert61instein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 104 Albert Einstein Coll Med 1300 Morris Pk Ave Bronx NY USA 10461 104
Citazione:
M.J. Martiney et al., "Suppressor mutations within the core binding factor (CBF/AML1) binding site of a T-cell lymphomagenic retrovirus", J VIROLOGY, 73(3), 1999, pp. 2143-2152

Abstract

The transcriptional enhancer of the lymphomagenic mouse retrovirus SL3 contains a binding site for the transcription factor core binding factor (CBF;also called AML1, PEBP2, and SEF1), The SL3 CBF binding site is called thecore. It differs from the core of the weakly lymphomagenic mouse retrovirus Akv by one nucleotide (the sequences are TGTGGTCAA and TGTGGTCAA, respectively). A mutant virus called SAA that was identical to SL3 except that itscore was mutated to the Akv sequence was only moderately attenuated for lymphomagenicity. In most SAA-infected mice, tumor proviruses contained either reversions of the original mutation or one of two novel core sequences. In 20% of the SAA-infected mice, tumor proviruses retained the original SAA/Akv core mutation but acquired one of two additional mutations (underlined), TG (C) under bar GGTCAA or TGTGGTC (T) under bar A, that generated core elements called So and T*, respectively. We tested whether the novel base changes in the So and T* cores were suppressor mutations. SL3 mutants that contained So or T* cores in place of the wild-type sequence were generated. These viruses induced T-cell lymphomas in mice more quickly than SAA, Therefore, the mutations in the So and T*: cores are indeed second-site suppressor mutations. The suppressor mutations increased CBF binding in vitro and transcriptional activity of the viral long terminal repeats (LTRs) in T lymphocytes to levels comparable to those of SL3. Thus, CBF binding was increased by any of three different nucleotide changes within the sequence of the SAA core. Increased CBF binding resulted in increased LTR transcriptional activity in T cells and in increased viral lymphomagenicity.

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Documento generato il 18/01/21 alle ore 14:22:45