SUG-1 Plays Proteolytic and Non-proteolytic Roles in the Control of Retinoic Acid Target Genes via Its Interaction with SRC-3
| Autor: | Maurizio Gianni, Enrico Garattini, Jean Luc Plassat, Ivan Raska, Sébastien Lalevée, Cécile Rochette-Egly, Nathalie Bruck, Christine Ferry |
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| Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Laboratorio di Biologia Molecolare, Istituto di Ricerche Farmacologiche Mario Negri, Peney, Maité, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
Proteasome Endopeptidase Complex
Transcription Genetic Receptors Retinoic Acid Retinoic acid Tretinoin Biology Models Biological Biochemistry Nuclear Receptor Coactivator 3 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chlorocebus aethiops Coactivator medicine Animals Humans Molecular Biology Transcription factor Adaptor Proteins Signal Transducing Histone Acetyltransferases 030304 developmental biology 0303 health sciences Retinoic Acid Receptor alpha Protein Synthesis Post-Translational Modification and Degradation Promoter Cell Biology LIM Domain Proteins Protein Structure Tertiary Retinoic acid receptor Gene Expression Regulation chemistry Proteasome 030220 oncology & carcinogenesis COS Cells Nuclear receptor coactivator 3 Trans-Activators ATPases Associated with Diverse Cellular Activities HeLa Cells Transcription Factors medicine.drug |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (12), pp.8127-35. ⟨10.1074/jbc.M808815200⟩ Journal of Biological Chemistry, 2009, 284 (12), pp.8127-35. ⟨10.1074/jbc.M808815200⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.m808815200 |
| Popis: | International audience; Nuclear retinoic acid receptor alpha (RARalpha) activates gene expression through dynamic interactions with coregulatory protein complexes, the assembly of which is directed by the ligand and the AF-2 domain of RARalpha. Then RARalpha and its coactivator SRC-3 are degraded by the proteasome. Recently it has emerged that the proteasome also plays a key role in RARalpha-mediated transcription. Here we show that SUG-1, one of the six ATPases of the 19 S regulatory complex of the 26 S proteasome, interacts with SRC-3, is recruited at the promoters of retinoic acid (RA) target genes, and thereby participates to their transcription. In addition, SUG-1 also mediates the proteasomal degradation of SRC-3. However, when present in excess amounts, SUG-1 blocks the activation of RARalpha target genes and the degradation of RARalpha that occurs in response to RA, via its ability to interfere with the recruitment of SRC-3 and other coregulators at the AF-2 domain of RARalpha. We propose a model in which the ratio between SUG-1 and SRC-3 is crucial for the control of RARalpha functioning. This study provides new insights into how SUG-1 has a unique role in linking the transcription and degradation processes via its ability to interact with SRC-3. |
| Databáze: | OpenAIRE |
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