A novel modulator domain of Ets transcription factors.
The ets gene family is composed of several oncogenes and codes for transcription factors. The Ets proteins have a similar sequence called the ets domain and bind to the core motif A/CGGAA. We show here that several members of the ets family have different trans-activating properties. The ets domain of Ets-1 is required for DNA binding. Adjacent to this domain there is a novel element that inhibits DNA binding. It appears to alter the structure of the DNA-binding domain before it interacts with DNA. There is a similar sequence in Ets-2 that also inhibits DNA binding. This sequence is absent in alternative splice products of h-Ets-1. PU1, the most distantly related member of the ets gene family, lacks this novel element. It has a distinct DNA-binding specificity that is determined by DNA sequences outside the core motif. These results have important implications for both the oncogenic and normal functions of ets family members.
Wasylyk
C
C
Centre National de la Recherche Scientifique-Laboratoire de Génétique Moléculaire des Eucaryotes/Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine, Strasbourg, France.
Kerckaert
J P
JP
Wasylyk
B
B
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011233:Precipitin Tests; D011487:Protein Conformation; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494041:ETS1 protein, human; C494069:ETS2 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA