The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells.

Kenney, Shannon C.; Holley-Guthrie, Elizabeth; Quinlivan, E. Byrd; Gutsch, David; Zhang, Qin; Bender, T.; Giot, Jean-François; Sergeant, Alain

doi:10.1128/mcb.12.1.136

Cited by 52 publications

(58 citation statements)

References 56 publications

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“…It has been reported that c-Myb can interact synergistically with the Epstein-Barr virus BZLF1 leucine zipper transactivator in lymphoid cells. This interaction occurs on the BZLF1 DNA binding site without DNA binding by c-Myb, although the DNA binding domain of c-Myb is required for the synergistic effect (36). It is also clear that c-Myb can transactivate promoters that lack Myb binding sites probably through interactions with particular types of TATA boxes (37).…”

Section: Discussionmentioning

confidence: 99%

A-Myb Up-regulates Bcl-2 through a Cdx Binding Site in t(14;18) Lymphoma Cells

Heckman

Mehew

Guo

et al. 2000

Journal of Biological Chemistry

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In follicular lymphoma, bcl-2 is translocated to the immunoglobulin heavy chain locus leading to deregulation of bcl-2 expression. We examined the role of Myb proteins in the regulation of bcl-2 expression in lymphoma cells. We showed that A-Myb up-regulates bcl-2 promoter activity. Northern and Western analyses demonstrated that A-Myb was expressed in the DHL-4 t(14; The bcl-2 gene was originally identified by its involvement in the t(14;18) translocation associated with human follicular lymphoma (1). The translocation of the bcl-2 gene from chromosome 18q to the immunoglobulin heavy chain locus at 14q results in the deregulated expression of bcl-2 (2). The overexpression of bcl-2 in t(14;18) lymphoma leads to high levels of bcl-2 mRNA and protein, which act to protect cells from apoptosis (3). During B cell development, bcl-2 is expressed at low levels in pre-B cells, in which extensive cell death occurs by apoptosis, whereas bcl-2 expression is higher in mature and activated B cells (3, 4). The mechanisms of normal and deregulated expression of bcl-2 remain unclear although recent studies have provided some insight. In t(14;18) cells, regulatory elements of both the bcl-2 promoter and the immunoglobulin heavy chain enhancers are believed to play a role in bcl-2 overexpression.18Two promoters mediate initiation of bcl-2 gene transcription. The 5Ј-promoter (P1) is located 1306 -1423 base pairs upstream of the translational start site (5). This is a TATA-less, GC-rich promoter that displays multiple start sites. The 3Ј-promoter (P2) is located 1.3 kilobases downstream of the P1 promoter (5). The P2 promoter contains a TATA-box and CCAAT element. A number of negative regulatory sites have been described in the bcl-2 promoter region. We have previously demonstrated three 1 binding sites, which function as negative regulators of bcl-2 expression in pre-B cells (6). The WT1 protein has also been shown to repress bcl-2 activity in HeLa cells and B cells (7,8). In addition, a negative regulatory element upstream of the P2 promoter has been described, although the proteins that bind to this element have not been identified (9). The p53 tumor suppressor has been shown to mediate repression of bcl-2 directly or indirectly through a 195-base pair region (10). We have also characterized a cyclic AMP (cAMP)-responsive element that is responsible for the positive regulation of bcl-2 expression during the activation of mature B cells and during the rescue of immature B cells from calcium-dependent apoptosis (11). In chicken myeloid cells, v-Myb was reported to function as an anti-apoptotic factor by up-regulation of bcl-2 expression, whereas in murine T cells, both c-Myb and B-Myb were shown to induce bcl-2 promoter activity (12-14). It is not clear if the Myb transcription factors have a similar function in human B cells.From our studies of the deregulation of bcl-2 in t(14;18) lymphoma cells, we have shown that the cAMP-response element site in the 5Ј-flanking sequence of the translocated bcl-2 gene is occupied (15). The cA...

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Section: Discussionmentioning

confidence: 99%

A-Myb Up-regulates Bcl-2 through a Cdx Binding Site in t(14;18) Lymphoma Cells

Heckman

Mehew

Guo

et al. 2000

Journal of Biological Chemistry

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“…Thus, c-Myb regulates lineagespeci®c genes although its expression is not lineage speci®c. Several transcription factors, such as Ets-12 (Dudek et al, 1992), CBF/PEBP2/AML1 (HernandezMunain andKrangel, 1994, 1995;Zaiman and Lenz, 1996) and BZLF1 (Kenney et al, 1992), can cooperate with c-Myb to activate speci®c enhancers or promoters. These proteins appear to cooperate without speci®cally binding to Myb, and the ability of c-Myb to cooperate with so many di erent transcription factors may be important for its role in controlling di erentiation.…”

Section: Proteins That Bind C-myb or V-mybmentioning

confidence: 99%

Myb binding proteins: regulators and cohorts in transformation

Ness

1999

Oncogene

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The c-Myb and v-Myb proteins are transcription factors that regulate cell proliferation and di erentiation. Both Myb proteins have been shown to interact with a number of cellular proteins, some of which are transcription factors that cooperate to activate speci®c promoters, while others regulate the transcriptional activity of Myb in speci®c contexts. By comparing and analysing the types of proteins that bind Myb, and the conserved domains of Myb that interact with other proteins, conclusions can be drawn regarding the role of speci®c partner proteins in the regulation of gene expression, cell proliferation and disease.

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“…Thus, c-Myb was shown to transactivate AP-1 through interaction with BZLF-1, the Z gene product of EBV. 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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The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells.

Cited by 52 publications

References 56 publications

A-Myb Up-regulates Bcl-2 through a Cdx Binding Site in t(14;18) Lymphoma Cells

A-Myb Up-regulates Bcl-2 through a Cdx Binding Site in t(14;18) Lymphoma Cells

Myb binding proteins: regulators and cohorts in transformation

The myb gene family in cell growth, differentiation and apoptosis

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