New human erg isoforms generated by alternative splicing are transcriptional activators.
The erg gene is a member of the ets gene family. ETS proteins have been shown to bind specifically the (GGA-A/T) motif and to transactivate via this consensus sequence. The human erg products exhibit approximately 70% homology with ETS proteins in their DNA-binding domain. We have isolated three erg cDNAs from a human fetal liver library. Two of them are different from the previously described erg-1 and erg-2 cDNAs (Rao et al., Science, 1987, 237, 635-639), in the middle of their coding sequence and in their 5' part where a novel initiation codon is introduced. These isoforms are generated by alternative RNA splicing from a single gene that leads to the inclusion or exclusion of different exon sequences. The three cDNAs expressed by an in vitro transcription-translation system direct the synthesis of proteins of approximately 38, 49 and 55 kDa. These in vitro erg products were tested for their DNA-binding activity by gel mobility-shift assays with different probes containing the ETS-specific binding site. The results indicated that all these erg isoforms are able to bind the ETS binding site in a specific manner. Our data using transient transfection assays indicate that erg protein isoforms function as transcriptional activators.
CNES URA 1160, Institut Pasteur, Lille, France.
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Duterque-Coquillaud
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C
Niel
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Plaza
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D
Stehelin
D016475:3T3 Cells; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051766:Early Growth Response Protein 1; D006801:Humans; D017874:Immediate-Early Proteins; D051379:Mice; D008969:Molecular Sequence Data; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; C072312:ERG protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D004247:DNA