1. Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response
- Author
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Marcel Boeglin, Christine Ferry, Samia Gaouar, Nicodème Paul, Benoit Fischer, Gabriella Pankotai-Bodo, Eric Samarut, Laurent Brino, Aleksandr Piskunov, and Cécile Rochette-Egly
- Subjects
Transcription, Genetic ,Retinoic acid ,Tretinoin ,Ubiquitin-conjugating enzyme ,F-box protein ,Nuclear Receptor Coactivator 3 ,chemistry.chemical_compound ,Cell Line, Tumor ,Chlorocebus aethiops ,Animals ,Humans ,Phosphorylation ,Cell Proliferation ,chemistry.chemical_classification ,Cell Nucleus ,DNA ligase ,Multidisciplinary ,Binding Sites ,biology ,Ubiquitin ,Cell Differentiation ,Biological Sciences ,Cullin Proteins ,Chromatin ,Ubiquitin ligase ,Biochemistry ,chemistry ,Microscopy, Fluorescence ,Nuclear receptor coactivator 3 ,COS Cells ,biology.protein ,Cullin - 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.
- Published
- 2011