Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains

• Published in: Oncogene Vol. 16; no. 25; pp. 3261 - 3268
• Main Authors: CARRERE, S, VERGER, A, FLOURENS, A, STEHELIN, D, DUTERQUE-COQUILLAUD, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 25-06-1998; Nature Publishing Group
• Subjects: Binding Sites; Biological and medical sciences; Biopolymers - chemistry; Deletion mutant; Dimerization; DNA-Binding Proteins - metabolism; ERG protein; FLI-1 protein; Fos protein; Fundamental and applied biological sciences. Psychology; Gene Deletion; Humans; Isoforms; Jun protein; Molecular and cellular biology; Molecular genetics; Mutation - genetics; Mutation - physiology; Oncogene Proteins - chemistry; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Proteins; Retroviridae Proteins, Oncogenic - chemistry; Retroviridae Proteins, Oncogenic - metabolism; Trans-Activators; Transcription Factor AP-1 - metabolism; Transcription factors; Transcription Factors - chemistry; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation - drug effects; Transcriptional Activation - genetics; Transcriptional Activation - physiology; Transcriptional Regulator ERG; Tumor Cells, Cultured; Human; Gene; Structure activity relation; Domain structure; C-Onc gene; DNA binding protein; Molecular interaction; Molecular complex; Dimerization; Heterodimer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1201868

The ets genes family encodes a group of proteins which function as transcription factors under physiological conditions. We report here that the Erg proteins, members of the Ets family, form homo and heterodimeric complexes in vitro. We demonstrate that the Ergp55 protein isoform forms dimers with itself and with the two other isoforms, Ergp49 and Ergp38. Using a set of Erg protein deletion mutants, we define two distinct domains independently involved in dimerization. The first one is located in the amino-terminal part of the protein containing the pointed domain (PNT), conserved in a subset of Ets proteins. The second one resides within the ETS domain, the DNA-binding domain. We also show that the Erg protein central region behaves as an inhibitory domain of dimerization and its removal enhances the Ergp55 transactivation properties. Furthermore, Ergp55 forms heterodimers with some other Ets proteins. Among the latter, we show that Fli-1, Ets-2, Er81 and Pu-1 physically interact with Erg. Finally, we show that the formation of the previously described ternary complex Ergp55/Fos/jun is mediated by ETS domain and Jun protein, while the ternary complex Ergp49/Fos/Jun is mediated by Fos protein.