Molecular cloning and characterization of human ERM, a new member of the Ets family closely related to mouse PEA3 and ER81 transcription factors.
The ets-related transcription factors PEA3 and ER81 have recently been isolated and characterized in the mouse. They share 95% identity in a 85 amino acid (AA) domain termed the ETS domain which is responsible for DNA binding, and therefore they form an Ets family group. By screening a human testis cDNA library with a probe containing the mouse PEA3 ETS domain, we isolated a 2.2 kb clone containing a 510 AA open reading frame. Since the ETS domain, which is localized in the carboxy terminal region of the encoded protein, is 95% and 96% identical to that of PEA3 and ER81, respectively, we named this new member 'Ets Related Molecule PEA3-like' (ERM). Although the first 120 AA in the amino-terminal region of ERM share 47% identity with PEA3 and 66% with ER81, ERM contains a central region of approximately 35 AA not found in the two mouse proteins. Gel shift analysis indicates that the full-length ERM protein is able to bind specifically to an oligonucleotide containing the consensus nucleotide core sequence GGAA recognized by the Ets proteins. Moreover, in vitro translation of 83 AA of the ERM ETS domain led to the production of a truncated protein which also binds to DNA. Though differential expression is observed in primary tumors and normal lymphocytes do not express ERM, this gene is almost ubiquitously expressed in human normal tissues. ERM mRNA is highly expressed in brain as well as in placenta and, to a lesser degree, in lung, pancreas, and heart. Moreover, almost all human cell lines tested express it at varying levels. In mouse tissues, we showed that PEA3 and ER81 mRNAs display restricted expression, whereas ERM is almost ubiquitously expressed as observed for human tissues. Altogether these results indicate that ERM is clearly a new ets family member and not the human equivalent of PEA3 or ER81.
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Unité d'Oncologie Molèculaire, CNRS URA 1160, Institut Pasteur de Lille, France.
Baert
J L
JL
Defossez
P A
PA
de Launoit
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Y
Stéhelin
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000032:analysis* / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000737:chemistry; D016415:Sequence Alignment; D014157:Transcription Factors / Q000032:analysis* / Q000737:chemistry
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; C513242:Etv5 protein, mouse; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors