Correlation of leukemogenic potential of murine retroviruses with transcriptional tissue preference of the viral long terminal repeats

Short, Mary K.; Okenquist, Sharon A.; Lenz, Jack

doi:10.1128/jvi.61.4.1067-1072.1987

Cited by 90 publications

(74 citation statements)

References 32 publications

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“…core II, and Mut. core I & II, containing the wild-type or mutated SL3 LTR linked to the chloramphenicol acetyltransferase (CAT) gene, were described previously (6,64,85,107). The mutated reporter plasmids Mut.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were harvested 30 h later, and lysates were prepared as previously described (6,85). One aliquot of the lysate was used to measure CAT enzymatic activity as previously described (30,85). The fraction of chloramphenicol that was acetylated was determined by PhosphorImager analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Transcriptional enhancers located within the long terminal repeats (LTRs) are the primary genetic determinants of the pathogenicity of murine leukemia viruses (MuLVs) (14,15,20,27,41,50,52,98). These elements determine the viral potency and the tissue specificity of viral leukemogenicity (13,85,92,98,105). SL3-3 (SL3) is an MuLV that induces T-cell lymphomas (74).…”

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confidence: 99%

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Transcriptional activation of a retrovirus enhancer by CBF (AML1) requires a second factor: evidence for cooperativity with c-Myb

Zaiman

Lenz

1996

J Virol

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Transcriptional enhancer sequences within the long terminal repeats (LTRs) of murine leukemia viruses are the primary genetic determinants of the tissue specificity and potency of the oncogenic potential of these retroviruses. SL3-3 (SL3) is a murine leukemia virus that induces T-cell lymphomas. The LTR enhancer of this virus contains two binding sites for the transcription factor CBF (also called AML1 and PEBP2) that flank binding sites for c-Myb and the Ets family of factors. Using cotransfection assays in P19 cells, we report here that CBF and c-Myb cooperatively stimulate transcription from the SL3 LTR. By itself, c-Myb had no stimulatory effect on transcription. However, when cotransfected with a cDNA encoding one form of the ␣ subunit of CBF called CBF␣2-451, a level of transactivation higher than that seen with CBF␣2-451 alone was detected. The negative regulatory domain near the carboxyl terminus of c-Myb did not affect this activity. Electrophoretic mobility shift assays indicated that CBF and c-Myb bind to DNA independently. Therefore, it appears that the cooperative stimulation of transcription by these factors occurs at a step in the process of transcription after the two factors are bound to the enhancer. Sequences near the carboxyl terminus of CBF␣2-451 were important for cooperativity with c-Myb, consistent with previous reports that this region contains an activation domain. However, CBF␣2-451 failed to activate transcription from a version of the SL3 LTR in which the enhancer was replaced with five tandem CBF-binding sites. Thus, it appears that transcriptional activation of the SL3 enhancer by CBF requires that an appropriate heterologous transcription factor be bound to a neighboring site in the regulatory sequences.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Transcriptional activation of a retrovirus enhancer by CBF (AML1) requires a second factor: evidence for cooperativity with c-Myb

Zaiman

Lenz

1996

J Virol

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“…Neither the Cbfa1 (Pebpa2a) nor Cbfa2 (AML1/Pebpa2b) gene is ex-VOL. 69,1995 ets AND cbf COOPERATION IN VIVO 4943 pressed in P19 cells (1,61). The ␤ subunit of CBF is expressed ubiquitously, and presumably this polypeptide was provided by the P19 cells.…”

Section: Cbf Stimulates Transcription From the Mo-mlv And Tcr␤mentioning

confidence: 99%

“…Mutations that disrupt the binding of ets and cbf proteins also attenuate induction (27,72). Third, the Mo-MLV enhancer is preferentially active in T cells (69), and mutations in the core site attenuate transcription from both the Mo-MLV and the related SL3-MLV enhancer preferentially in T cells (6,72,77). Mutations in the LVb site attenuate the constitutive activity of the Mo-MLV enhancer in multiple cell types, including T cells (27,72).…”

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confidence: 99%

Transactivation of the Moloney murine leukemia virus and T-cell receptor beta-chain enhancers by cbf and ets requires intact binding sites for both proteins

Sun

Graves

Speck

1995

J Virol

138

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The Moloney murine leukemia virus (Mo-MLV) enhancer contains binding sites (LVb and LVc) for the ets gene family of proteins and a core site that binds the polyomavirus enhancer-binding protein 2/core-binding factor (cbf) family of proteins. The LVb and core sites in the Mo-MLV enhancer contribute to its constitutive activity in T cells. All three binding sites (LVb, LVc, and core) are required for phorbol ester inducibility of the Mo-MLV enhancer. Adjacent binding sites for the ets and cbf proteins likewise constitute a phorbol ester response element within the human T-cell receptor ␤-chain (TCR␤) enhancer and contribute to constitutive transcriptional activity of the TCR␤ enhancer in T cells. Here we show that the CBF␣ subunit encoded by the mouse Cbfa2 gene (the murine homolog of human AML1) and three ets proteins, Ets-1, Ets-2, and GA-binding protein (GABP), transactivate both the Mo-MLV and mouse TCR␤ enhancer in transient-expression assays. Moreover, we show that transactivation by Cbf␣2 requires both intact ets and cbf binding sites. Transactivation by Ets-1, Ets-2, and GABP likewise requires intact binding sites for ets proteins and CBF. Supportive biochemical analyses demonstrate that both proteins can bind simultaneously to a composite enhancer element. These findings suggest that ets and cbf proteins cooperate in vivo to regulate transcription from the Mo-MLV and TCR␤ enhancers.

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Nuclear Factors That Bind to the U3 Region of Two Murine Myeloid Leukemia-Inducing Retroviruses, Cas-Br-E and Graffi

Barat

Rassart

1998

Virology

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Cas-Br-E and Graffi are two myeloid leukemia-inducing murine viruses. Cas-Br-E induces, in NIH-Swiss mice, mostly non-T, non-B leukemia composed of very immature cells with no specific characteristics (Bergeron et al. (1993). Leukemia 7, 954-962). The Graffi murine leukemia virus causes exclusively myeloid leukemia, but the tumor cells are clearly of granulocytic nature (Ru et al. (1993). J. Virol. 67, 4722). We were interested to understand the role of the long terminal repeat (LTR) U3 region in the myeloid specificity of these two retroviruses. We used DNase I footprinting and gel mobility shift assays to identify a number of protein binding sites within Cas-Br-E and Graffi U3 regions. The pattern of protected regions is highly similar for the two viruses. Some factors identified in other murine leukemia viruses, like the core binding factor, also bind to Cas-Br-E and Graffi LTR; however, other binding sites seem specific for these two viruses. Only one difference between them was noted, at the 5' end of the U3 region. Transcriptional activity of both LTRs was also analyzed in various cell lines and compared with other murine leukemia viruses. The results show a slight myeloid specificity for the two LTRs, and indicate that the Graffi enhancer is quite strong in a broad range of cell types.

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Correlation of leukemogenic potential of murine retroviruses with transcriptional tissue preference of the viral long terminal repeats

Cited by 90 publications

References 32 publications

Transcriptional activation of a retrovirus enhancer by CBF (AML1) requires a second factor: evidence for cooperativity with c-Myb

Transcriptional activation of a retrovirus enhancer by CBF (AML1) requires a second factor: evidence for cooperativity with c-Myb

Transactivation of the Moloney murine leukemia virus and T-cell receptor beta-chain enhancers by cbf and ets requires intact binding sites for both proteins

Nuclear Factors That Bind to the U3 Region of Two Murine Myeloid Leukemia-Inducing Retroviruses, Cas-Br-E and Graffi

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