ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development.

López, Manuel Carlos López; Oettgen, Peter; Akbarali, Yasmin; Dendorfer, U; Libermann, Towia A.

doi:10.1128/mcb.14.5.3292

Cited by 117 publications

(131 citation statements)

References 88 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…Analyses of human and mouse Fli-1 cDNA sequences placed them in the ETS gene family which shows high homology within their DNA binding (ETS) domain (Ben-David et al, 1991;Prasad et al, 1992) and codes for di erent sequence-speci®c transcriptional activators. The superfamily of ETS genes includes several members: c-ets-1 (Reddy and Rao, 1988;Chen, 1988), ets-2 Boulukos et al, 1988), erg Rao et al, 1987), Elk-1 and Elk-2 (Rao et al, 1989), Pu.1/Spi-1 and Spi-1B (Goebl et al, 1990;Klemsz et al, 1990;Ray et al, 1992), E-74 (Burtis et al, 1990) Sap-1 and Sap-2 (Dalton and Triesman, 1992), GABP a (LaMarco et al, 1991), Elf-1 , PEA-3 (Xin et al, 1992), Fli-1 (Ben-David et al, 1990;Prasad et al, 1992), D-elg (Pribyl et al, 1988), ER-81 and ER-71 (Brown and McKnight, 1992), Tel (Golub et al, 1994), ERP (Lopez et al, 1994) and ETV-1 (Jeon et al, 1995). Most of the ETS proteins are related to each other by virtue of their Etsdomain, a 85-residue region capable of binding to speci®c DNA binding sequences.…”

Section: Introductionmentioning

confidence: 99%

Fli-1b is generated by usage of differential splicing and alternative promoter

et al. 1998

View full text Add to dashboard Cite

The proto-oncogene Fli-1, a member of Ets family is rearranged or activated through proviral integration in erythroleukemias, induced by Friends' Murine Leukemia Virus. The DNA binding domain (ETS domain) of Fli-1 is fused to the RNA binding domain of EWS by t(11q24:22q12) chromosomal translocation in Ewing's sarcoma and primitive neuroectodermal tumors. Screening of human cDNA libraries has identi®ed two di erent 5'-termini and alternatively spliced forms of the human Fli-1 gene (Fli-1b), suggesting the possible existence of two independent promoters. The genomic sequence adjacent to the alternate exon of human Fli-1b gene shows functional promoter activity when cloned in promoter-less CAT expression vector and transfected into QT-6 cells. The transcription initiation (CAP) site and minimum promoter region necessary for function were localized. The 5'-¯anking regions of human Fli-1b and mouse Fli-1 show 80% homology suggesting conserved promoter regulatory elements. The Fli-1b 5'-anking sequence lacks canonical TATA or CCAAT boxes but contains a partially conserved TATA-like sequence at position 242. Several transcription factor binding sequences like ATF/CREB, E2A-PBX1, EBP, PEA-3, ETS-2, Sp-1, c-Myc, TBP, GATA-1 and Oct-3 were conserved in the promoter sequence. Functional promoter assays revealed that Fli-1b promoter shows very strong transcriptional activation compared to Fli-1 promoter. We also showed that variant Fli-1b has transcriptional activation properties similar to those of Fli-1. Fli-1b and Fli-1 show di erential expression in various hematopoietic cell lines. This di erential expression and promoter activities of Fli-1 and Fli-1b suggests that several mechanisms are involved in Fli-1 gene regulation which are mediated by many transcription factors.

show abstract

Section: Introductionmentioning

confidence: 99%

Fli-1b is generated by usage of differential splicing and alternative promoter

et al. 1998

View full text Add to dashboard Cite

show abstract

“…The TCF's which includes Elk-1 have three domains with similar sequences and functions. The ets domain mediates DNA binding, the SRF interaction domain interacts with SRF to form a ternary complex with the c-fos SRE and the C-terminal domain activates transcription upon phosphorylation by MAP kinases (Rao et al, 1989;Rao and Reddy, 1992;Dalton and Treisman, 1992;Janknecht et al, 1993Janknecht et al, , 1994Marias et al, 1993;Giovane et al, 1994;Hipskind et al, 1994;Kortenjann et al, 1994;Lopez et al, 1994;Hill et al, 1995;Price et al, 1995;Whitmarsh et al, 1995) and JNK kinases (Gupta et al, 1996). Thus Elk-1 represents a key link between signal transduction and induction of gene transcription.…”

mentioning

confidence: 99%

“…Elk-1, SAP1, and NET/ ERP/SAP2/Elk-3 (Rao et al, 1989;Hipskind et al, 1991;Giovane et al, 1994;Lopez et al, 1994;Dalton and Treisman, 1992;Price et al, 1995;Nozaki et al, 1996). The Elk-1 gene codes for at least two alternately spliced products Elk-1 (Rao et al, 1989) and DElk-1 (Rao and Reddy, 1993) which function as transcriptional activators (Rao and Reddy, 1992;Bhattacharya et al, 1993), are substrates for MAP kinases Marias et al, 1993;Hill et al, 1993) and JNK protein kinases (Gupta et al, 1996;Whitmarsh et al, 1995).…”

mentioning

confidence: 99%

Induction of apoptosis by Elk-1 and ΔElk-1 proteins

et al. 1998

View full text Add to dashboard Cite

Elk-1, an ets related gene codes for at least two splice variants Elk-1, which regulates c-fos transcription and DElk-1, both of which function as transcriptional activators. To investigate the role of Elk-1 and DElk-1 proteins in apoptosis; we have developed rat ®broblast cell lines and human breast cancer cell lines expressing Elk-1 and DElk-1. The expression of Elk-1 and DElk-1 proteins in the Elk-1/DElk-1 transfectants were analysed by immuno¯uorescence, immunohistochemistry, and Western blot analysis. The Elk-1 unlike DElk-1 transfectants showed a shortened and¯attened morphology compared to the parental cells. We have found that calcium ionophore treatment of Rat-1 Elk-1, MCF-7 Elk-1, Rat-1 DElk-1 and MCF-7 DElk-1 transfectants resulted in programmed cell death. These results indicate that constitutive expression of Elk-1 and DElk-1 proteins triggers apoptosis in Rat-1 ®broblasts and breast cancer cells when treated with calcium ionophore.Keywords: Elk-1; DElk-1; apoptosis; calcium ionophore; breast cancer; MCF-7; Rat-1The Elk-1 gene belongs to the ets family of ternary complex factors (TCFs), i.e. Elk-1, SAP1, and NET/ ERP/SAP2/Elk-3 (Rao et al., 1989;Hipskind et al., 1991;Giovane et al., 1994;Lopez et al., 1994;Dalton and Treisman, 1992;Price et al., 1995;Nozaki et al., 1996). The Elk-1 gene codes for at least two alternately spliced products Elk-1 (Rao et al., 1989) and DElk-1 (Rao and Reddy, 1993) which function as transcriptional activators (Rao and Reddy, 1992;Bhattacharya et al., 1993), are substrates for MAP kinases Marias et al., 1993;Hill et al., 1993) and JNK protein kinases (Gupta et al., 1996;Whitmarsh et al., 1995). As mentioned earlier, the Elk-1 protein is a TCF which in association with serum response factor (SRF) forms a ternary complex on the serum response element (SRE) of the c-fos promoter and regulates cfos transcription (Hipskind et al., 1991). The TCF's which includes Elk-1 have three domains with similar sequences and functions. The ets domain mediates DNA binding, the SRF interaction domain interacts with SRF to form a ternary complex with the c-fos SRE and the C-terminal domain activates transcription upon phosphorylation by MAP kinases (Rao et al., 1989;Rao and Reddy, 1992;Dalton and Treisman, 1992;Janknecht et al., 1993Janknecht et al., , 1994Marias et al., 1993;Giovane et al., 1994;Hipskind et al., 1994;Kortenjann et al., 1994;Lopez et al., 1994;Hill et al., 1995;Price et al., 1995;Whitmarsh et al., 1995) and JNK kinases (Gupta et al., 1996). Thus Elk-1 represents a key link between signal transduction and induction of gene transcription.The Gag-Myb-Ets fusion protein, identi®ed in the avian acute leukemia virus E26 was shown to inhibit apoptosis and induce erythroid di erentiation in hematopoietic cells (Athanasiou et al., 1996). Similarly the Ets-1 proto-oncogene was shown to be required for the normal survival and activation of B and T cells while an Ets-1 splice variant was shown to induce apoptosis in human colon cancer cells indicating a role in apoptosis (Bories et al....

show abstract

“…Mutation of the E3 element in 70 results in a more drastic reduction of activity compared to the corresponding mutation in 170. Based on these results we have proposed that the A and B elements define a minimal enhancer whose activity is raised by the presence of proximal E motifs (14).The A and B sites bind members of the ETS domain protein family (14,26,27). Binding of the B cell and macrophage-specific factor PU.1 to the wild type B element and a panel of three nucleotide substitution mutants within the element correlates with the ability of the mutants to activate transcription.…”

mentioning

confidence: 99%

A Three-protein-DNA Complex on a B Cell-specific Domain of the Immunoglobulin μ Heavy Chain Gene Enhancer

Rao

Dang

Tian³

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

The lymphoid-specific immunoglobulin heavy chain gene intron enhancer ( E) contains multiple binding sites for trans-acting nuclear factors. We have used a combination of in vitro and in vivo assays to reconstruct protein-DNA interactions on a minimal B cell-specific enhancer that contains three motifs, A, B, and E3. Using ETS-domain proteins that transactivate the minimal enhancer in non-lymphoid cells, we show that (i) PU.1 binds coordinately to both A and B sites in vitro and (ii) in the presence of Ets-1, this factor binds to the A site and PU.1 to the B site. Two factors, TFE3 and USF, bind to the E3 element. When the ETS proteins are present together with E3 binding proteins, a threeprotein-DNA complex is generated. Furthermore, we provide evidence for protein-protein interactions between Ets-1 and PU.1 proteins that bind to A and B sites, and between Ets-1 and TFE3 bound to the A and E3 sites. We propose that this domain of the enhancer is assembled into a nucleoprotein complex that contains two tissue-restricted ETS domain proteins that recognize DNA from the same side of the helix and one ubiquitously expressed bHLH-leucine zipper protein that binds between them, recognizing its site from a different side of the helix. The immunoglobulinheavy chain (IgH) gene intron enhancer is a tissue-specific regulatory element that is necessary for expression of the IgH gene (1, 2). Since the proposal of Alt and colleagues of the correlation between transcription and immunoglobulin gene rearrangements (3-5), the enhancer has been considered a likely candidate to be the sequence that regulates rearrangements at this locus. Recently, this hypothesis has been directly verified in mice containing disrupted enhancer alleles (6, 7). Thus, the enhancer is activated at very early stages of B cell differentiation, prior to the onset of D H to J H rearrangements. In addition, experiments in transgenic mice have shown that this enhancer is sufficient to direct expression of heterologous genes in B and T lymphoid cells (8 -11).The enhancer contains binding sites for multiple DNA binding proteins, and tissue-specific activity has been proposed to be the consequence of both positive and negative regulatory proteins. Positive regulation is effected by lymphoid-specific transcription activators, such as those that bind to the A, B (12-15), and octamer elements (16 -18). Negative regulation is effected by proteins found in non-lymphoid cells that may suppress enhancer activity (19 -22), such as those that bind to the E5 site within the enhancer (23, 24). In addition, there are several sites within the enhancer referred to as E motifs. These elements, E1-E5, fit the consensus CANNTG and bind proteins belonging to the basic helix-loop-helix family of transcription factors (25) that are expressed in both lymphoid and nonlymphoid cells. We have previously shown that mutation of either A or B elements abrogates B cell-specific activity of a 170 nucleotide enhancer ( 170) that contains both these elements as well as E1, E3, and E5. Mutati...

show abstract

ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development.

Cited by 117 publications

References 88 publications

Fli-1b is generated by usage of differential splicing and alternative promoter

Fli-1b is generated by usage of differential splicing and alternative promoter

Induction of apoptosis by Elk-1 and ΔElk-1 proteins

A Three-protein-DNA Complex on a B Cell-specific Domain of the Immunoglobulin μ Heavy Chain Gene Enhancer

Contact Info

Product

Resources

About