title: Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response.
abstract: SRC-3 is an important coactivator of nuclear receptors including the retinoic acid (RA) receptor α. Most of SRC-3 functions are facilitated by changes in the posttranslational code of the protein that involves mainly phosphorylation and ubiquitination. We recently reported that SRC-3 is degraded by the proteasome in response to RA. Here, by using an RNAi E3-ubiquitin ligase entry screen, we identified CUL-3 and RBX1 as components of the E3 ubiquitin ligase involved in the RA-induced ubiquitination and subsequent degradation of SRC-3. We also show that the RA-induced ubiquitination of SRC-3 depends on its prior phosphorylation at serine 860 that promotes binding of the CUL-3-based E3 ligase in the nucleus. Finally, phosphorylation, ubiquitination, and degradation of SRC-3 cooperate to control the dynamics of transcription. In all, this process participates to the antiproliferative effect of RA.
authors.affiliation: Department of Functional Genomics and Cancer, Institut National de la Santé et de la Recherche Médicale U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, Université de Strasbourg, BP 10142, 67404 Illkirch Cedex, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Ferry
authors.forename: Samia
authors.initials: S
authors.lastname: Gaouar
authors.forename: Benoit
authors.initials: B
authors.lastname: Fischer
authors.forename: Marcel
authors.initials: M
authors.lastname: Boeglin
authors.forename: Nicodeme
authors.initials: N
authors.lastname: Paul
authors.forename: Eric
authors.initials: E
authors.lastname: Samarut
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Piskunov
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pankotai-Bodo
authors.forename: Laurent
authors.initials: L
authors.lastname: Brino
authors.forename: Cecile
authors.initials: C
authors.lastname: Rochette-Egly
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000737:chemistry; D044842:Cullin Proteins / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism*; D010766:Phosphorylation; D014158:Transcription, Genetic; D014212:Tretinoin / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry*
chemical_list: C503645:CUL3 protein, human; D002843:Chromatin; D044842:Cullin Proteins; D025801:Ubiquitin; D014212:Tretinoin; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3