SUG-1 plays proteolytic and non-proteolytic roles in the control of retinoic acid target genes via its interaction with SRC-3.

Abstract : 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.
Type de document :
Article dans une revue
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (12), pp.8127-35. 〈10.1074/jbc.M808815200〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00383334
Contributeur : Maité Peney <>
Soumis le : mardi 12 mai 2009 - 18:11:06
Dernière modification le : jeudi 11 janvier 2018 - 06:17:43

Lien texte intégral

Identifiants

Collections

Citation

Christine Ferry, Maurizio Gianni, Sébastien Lalevée, Nathalie Bruck, Jean-Luc Plassat, et al.. SUG-1 plays proteolytic and non-proteolytic roles in the control of retinoic acid target genes via its interaction with SRC-3.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (12), pp.8127-35. 〈10.1074/jbc.M808815200〉. 〈inserm-00383334〉

Partager

Métriques

Consultations de la notice

192