Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation
| Autor: | Véronique Fafeur, Jean-Luc Baert, Cindy Degerny, J. Coll, N. Vintonenko, Bénédicte Foveau, David Tulasne, Zongling Ji, Julien Deheuninck, Catherine Leroy |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
SENP1 Transcription Genetic Lysine Immunoblotting SUMO-1 Protein SUMO protein SUMO enzymes Kidney Cell Line Proto-Oncogene Protein c-ets-1 Dogs Ubiquitin Chlorocebus aethiops Genetics Animals Humans Immunoprecipitation Luciferases Molecular Biology Transcription factor biology Kidney metabolism Molecular biology Cell biology Proteasome COS Cells Ubiquitin-Conjugating Enzymes biology.protein Rabbits Protein Processing Post-Translational |
| Zdroj: | Oncogene. 26(3) |
| ISSN: | 0950-9232 |
| Popis: | Sumoylation and ubiquitinylation reversibly regulate the activity of transcription factors through covalent attachment to lysine residues of target proteins. We examined whether the Ets-1 transcription factor is modified by sumoylation and/or ubiquitinylation. Among four potential SUMO motifs in Ets-1, we identified lysines 15 and 227 within the LK(15)YE and IK(227)QE motifs, as being the sumoylation acceptor sites. Using transfection of Ets-1 wildtype (WT) or its sumoylation deficient version (Ets-1 K15R/K227R), as well as WT or mutant proteins of the SUMO pathway, we further demonstrated that the E2 SUMO-conjugating enzyme Ubc9 and a E3 SUMO ligase, PIASy, can enhance Ets-1 sumoylation, while a SUMO protease, SENP1, can desumoylate Ets-1. We also found that Ets-1 is modified by K48-linked polyubiquitinylation independently of the sumoylation acceptor sites and is degraded through the 26S proteasome pathway, while sumoylation of Ets-1 does not affect its stability. Finally, sumoylation of Ets-1 leads to reduced transactivation and we demonstrated that previously identified critical lysine residues in Synergistic Control motifs are the sumoylation acceptor sites of Ets-1. These data show that Ets-1 can be modified by sumoylation and/or ubiquitinylation, with sumoylation repressing transcriptional activity of Ets-1 and having no clear antagonistic action on the ubiquitin-proteasome degradation pathway. |
| Databáze: | OpenAIRE |
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