Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription.

Dasgupta, Purandar; Saikumar, Pothana; Reddy, C. Devendranath; Reddy, E. Premkumar

doi:10.1073/pnas.87.20.8090

Cited by 65 publications

(49 citation statements)

References 36 publications

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“…6). c-Myb has been reported to be augmented by Akt (45) and to be capable of transactivating the long terminal repeat promoter of retrovirus (47). Thus it is conceivable that c-Myb is responsible for the up-regulation of Akt/EGFP.…”

Section: Discussionmentioning

confidence: 99%

Akt Is a Neutral Amplifier for Th Cell Differentiation

Arimura

Shiroki

Kuwahara

et al. 2004

Journal of Biological Chemistry

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Both CD28 and its relative, inducible costimulator (ICOS), have a binding motif for phosphatidylinositol 3-kinase (PI3K) in their cytoplasmic tail, and the binding of PI3K leads to activation of a serine/threonine kinase, Akt. The role of Akt in cytokine production and helper T (Th) cell differentiation remains obscure. In this study, we found that enforced expression of the constitutively active form (E40K) of Akt rendered CD4 ؉ T cells activated. Wild-type of Akt and E40K promoted Th1 cell differentiation in C57BL/6-derived and Th1-polarized BALB/c-derived CD4 ؉ T cells, while both promoted Th2 cell differentiation in BALB/c-derived and Th2-polarized C57BL/6 CD4 ؉ T cells. E40K also facilitated Th1 differentiation in CD4 ؉ T cells from IL-4-deficient mice with the BALB/c background. E40K up-regulated expression of NF-AT and c-Myb, which may be related to the augmentation of cytokine production by E40K. These findings indicate that the mechanism by which Akt augments cytokine production via CD28 and ICOS is Th cell type-specific and reflects the intracellular status affected by the cytokine milieu. We conclude that Akt is a neutral amplifier of T cell activation and Th differentiation.

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Section: Discussionmentioning

confidence: 99%

Akt Is a Neutral Amplifier for Th Cell Differentiation

Arimura

Shiroki

Kuwahara

et al. 2004

Journal of Biological Chemistry

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“…The silencing and enhancer activities correlate with the binding of Max-Mad1 and of USF, respectively (71). Finally, four E boxes are present in the promoter region of human immunodeficiency virus type 1 (HIV-1) (51,52,(132)(133)(134)(135), and cooperative interaction of USF1 with Ets-1 is required for full transcriptional activity of the HIV-1 LTR in T-cells (104).…”

Section: Discussionmentioning

confidence: 99%

Upstream Stimulatory Factors Binding to an E Box Motif in the R Region of the Bovine Leukemia Virus Long Terminal Repeat Stimulates Viral Gene Expression

Calomme¹,

Nguyên²,

Launoit³

et al. 2002

Journal of Biological Chemistry

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The bovine leukemia virus (BLV) promoter is located in its 5-long terminal repeat and is composed of the U3, R, and U5 regions. BLV transcription is regulated by cis-acting elements located in the U3 region, including three 21-bp enhancers required for transactivation of the BLV promoter by the virus-encoded transactivator Tax BLV . In addition to the U3 cis-acting elements, both the R and U5 regions contain stimulatory sequences. To date, no transcription factor-binding site has been identified in the R region. Here sequence analysis of this region revealed the presence of a potential E box motif (5-CACGTG-3). By competition and supershift gel shift assays, we demonstrated that the basic helix-loop-helix transcription factors USF1 and USF2 specifically interacted with this R region E box motif. Mutations abolishing upstream stimulatory factor (USF) binding caused a reproducible decrease in basal or Tax-activated BLV promoter-driven gene expression in transient transfection assays of B-lymphoid cell lines. Cotransfection experiments showed that the USF1 and USF2a transactivators were able to act through the BLV R region E box. Taken together, these results physically and functionally characterize a USF-binding site in the R region of BLV. This E box motif located downstream of the transcription start site constitutes a new positive regulatory element involved in the transcriptional activity of the BLV promoter and could play an important role in virus replication. Bovine leukemia virus (BLV)1 is a B-lymphotropic oncogenic retrovirus that infects cattle and is associated with enzootic bovine leukosis, a neoplastic proliferation of B-cells (1-6). BLV is closely related to human T-lymphotropic viruses HTLV-I and -II. The majority of BLV-infected cattle are asymptomatic carriers of the virus. Only about 30% of BLV-infected animals develop a preneoplastic condition termed persistent lymphocytosis, with 2-5% developing B-cell leukemia and/or lymphoma after a long latency period. The virus can be experimentally transmitted to sheep, in which it causes similar pathologies, providing a helpful model to understand BLV and HTLV-induced leukemogenesis. BLV infection is characterized by viral latency in the large majority of infected cells and by the absence of viremia. These features are thought to be due to the transcriptional repression of viral expression in vivo (7-9). The latency is likely to be a viral strategy to escape the host immune response and allow tumor development.BLV transcription initiates at the unique promoter located in the 5Ј-long terminal repeat (5Ј-LTR) of the BLV genome. The 5Ј-LTR is composed of the U3, R, and U5 regions and transcription initiates at the U3-R junction. The U3 region contains the main sites that regulate viral transcription (Fig. 1) as follows: the promoter CAAT and TATA boxes (10, 11), a glucocorticoidresponsive element (12-15), and a large segment protected in DNase footprinting assays containing NF-B-related sites (16,17). Among the most important sites are three copies of an imp...

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“…In this case, BZLF was found to transactivate transcription via the AP-1 site only when complexed with c-Myb (Kenney et al, 1992). Mybmediated transactivation of HIV and HTLV-1 promoters has been reported (Dasgupta et al, 1990(Dasgupta et al, , 1992.…”

Section: The Cellular Target Genes Of Mybmentioning

confidence: 99%

The myb gene family in cell growth, differentiation and apoptosis

1999

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The myb gene family consists of three members, named A, B and c-myb which encode nuclear proteins that function as transcriptional transactivators. Proteins encoded by these three genes exhibit a tripartate structure with an N-terminal DNA-binding domain, a central transactivation domain and a C-terminal regulatory domain. These proteins exhibit highest homology in their DNA binding domains and appear to bind DNA with overlapping sequence speci®cities. Transactivation by myb gene family varies considerably depending on cell type and promoter context suggesting a dependence on interaction with other cell type speci®c co-factors. While the C-terminal domains of A-Myb and c-Myb proteins exert a negative regulatory eect on their transcriptional transactivation function, the C-terminal domain of BMyb appears to function as a positive regulator of this activity. One or more of these proteins interact with other transcription factors such as Ets-2, CEBP and NF-M. In addition, expression of these genes is cell cycleregulated and inhibition of their expression with antisense oligonucleotides has been found to aect cell cycleprogression, cell division and/or dierentiation. Members of the myb gene family exhibit dierent temporal and spatial expression patterns suggesting a distinctive function for each of these genes. Gene knockout experiments show that these genes play an essential role in development. Loss of c-myb function results in embryonic lethality due to failure of fetal hepatic hematopoiesis. A-myb null mutant mice, on the other hand are viable but exhibit growth abnormalities, and defects in spermatogenesis and female breast development. While the role of c-myb in oncogenesis is well established, future experiments are likely to provide further clues regarding the role of A-myb and B-myb in tumorigenesis.

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Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription.

Cited by 65 publications

References 36 publications

Akt Is a Neutral Amplifier for Th Cell Differentiation

Akt Is a Neutral Amplifier for Th Cell Differentiation

Upstream Stimulatory Factors Binding to an E Box Motif in the R Region of the Bovine Leukemia Virus Long Terminal Repeat Stimulates Viral Gene Expression

The myb gene family in cell growth, differentiation and apoptosis

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