Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells.

Xin, Ji-Hou; Cowie, Alison; Lachance, Paul; Hassell, John A.

doi:10.1101/gad.6.3.481

Cited by 331 publications

(247 citation statements)

References 71 publications

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“…A second in-frame ATG signal is located nine nucleotides downstream. Both translation initiation signals possess good Kozak consensus sequences (Kozak, 1991) and are conserved at the second and third ATGs of the mouse PEA3 cDNA (Figure 2; Xin et al, 1992). However, as ribosomes are thought to locate their initiation sites by scanning, the ®rst initiation signal is likely to be the functionally important one (Kozak, 1991).…”

Section: Resultsmentioning

confidence: 99%

“…The PEA3 subfamily is composed of three members PEA3, ERM and ER81 in both humans and mice (Xin et al, 1992;Higashino et al, 1993;MonteÂ et al, 1994MonteÂ et al, , 1995Brown and McKnight, 1992;Chotteau-Lelievre et al, 1997). Members of this subfamily share considerable sequence homology.…”

Section: Introductionmentioning

confidence: 99%

“…However, the binding speci®city of PEA3 subfamily members has not been investigated in detail. DNA binding by full-length murine PEA3 (Xin et al, 1992) and human ERM (Laget et al, 1996) is inhibited by sequences outside the conserved ETS-domain.…”

Section: Introductionmentioning

confidence: 99%

“…In adults, PEA3 subfamily members exhibit overlapping expression patterns. For example, all three family members are highly expressed in the brain whereas in comparison to ERM, ER81 shows di erential expression and is strongly expressed in the heart but only weakly expressed in placenta (Xin et al, 1992;MonteÂ et al, 1994MonteÂ et al, , 1995Brown and McKnight, 1992). However, to date, it is unclear whether these transcription factors are expressed during early development and whether they play a role in regulating developmental processes.…”

Section: Introductionmentioning

confidence: 99%

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Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor

et al. 1998

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The PEA3 subfamily of ETS-domain proteins play important roles in regulating transcriptional activation and have been implicated in several tumorigenic processes. Here we describe the identi®cation of a further member of this family from zebra®sh which most likely represents a homologue of PEA3. A high degree of sequence conservation is observed in the ETS DNAbinding domain and acidic transcriptional activation domain. The DNA binding speci®city of zebra®sh PEA3 is virtually identical to that exhibited by mammalian family members and is autoregulated by cisacting inhibitory domains. Transcriptional activation by zebra®sh PEA3 is potentiated by the ERK MAP kinase and protein kinase A pathways. During embryogenesis, PEA3 is expressed in complex spatial and temporal patterns in both mesodermal somites and ectodermal tissues including the brain, dorsal spinal chord and neural crest. Our characterisation of zebra®sh PEA3 furthers our understanding of its molecular function and its expression pro®le suggests a novel role in cell patterning in the early vertebrate embryo.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor

et al. 1998

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“…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

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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.

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Expression of the PEA3 group of ETS-related transcription factors in human breast-cancer cells

et al. 1997

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The PEA3 group of transcription factors belongs to the ets family and is composed of 3 known members, PEA3, ERM and ER81, which are more than 95% identical within the DNA-binding ETS domain and exhibit 50% aa identity overall. Recently, transgenic mice bearing the c-erbB-2/neu oncogene have been shown to over-express PEA3 mRNA in mammary adenocarcinomas, suggesting a role for this gene family in mammary tumorigenesis. In the present work we characterized the mRNA expression levels of PEA3-group genes in a series of human epithelial breast cell lines. Each of the 3 genes was highly expressed in normal human HMEC 1001-7 and HMEC 219-4 cells. In breast-cancer cell lines, the 3 genes were highly expressed in the ER- MDA-MB-436, MDA-MB-330, MDA-MB-231 and BT-20 cell lines, but not in the ER+ MDA-MB-134-VI and ZR-75-1 cells. In an attempt to characterize the PEA3-group proteins in breast-cancer cells, we first produced and characterized specific antibodies against each of these 3 proteins. The anti-ERM and anti-ER81 antibodies recognized specific strong bands at approximately 72 kDa and 62 kDa, corresponding to ERM and ER81, respectively, in MDA-MB-231 and Hs-578T cells expressing significant levels of the 3 mRNAs. No protein was detected in MCF-7 cells expressing low levels of mRNA for PEA3-group-family genes, or in ZR-75-1 cells, where mRNA was undetectable by Northern blot. Although in vitro-translated PEA3 is specifically immunoprecipitated by anti-PEA3 anti-serum, we were unable to immunoprecipitate PEA3 protein from MDA-MB-231 and Hs-578T cells. In order to study the transcription factor activity of ERM, PEA3 and ER81 proteins in mammary-cancer cells, we tested their ability to transactivate a reporter plasmid containing 3 Ets-binding sites, and were able to show that, in all the breast-cancer cells tested, transfected ERM, PEA3 and ER81 are able to transactivate. Although the target genes of the PEA3 group of transcription factors in breast-cancer cells have yet to be determined, these genes have a potential role in the regulation of growth and the progression of human breast cancer.

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Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells.

Cited by 331 publications

References 71 publications

Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor

Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor

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

Expression of the PEA3 group of ETS-related transcription factors in human breast-cancer cells

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