Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response

Christine Ferry (1) , Samia Gaouar (1) , Benoit Fischer (1) , Marcel Boeglin (1) , Nicodème Paul (2) , Eric Samarut (1) , Aleksandr Piskunov (1) , Gabriella Pankotai-Bodo (1) , Laurent Brino (1) , Cécile Rochette-Egly (1)

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
2 Inserm U964 - CNRS UMR7104 - IGBMC - Centre for Integrative Biology - CBI

SRC-3 is an important coactivator of nuclear receptors including the retinoic acid (RA) receptor alpha. 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.

Domaines: Biochimie, Biologie Moléculaire

Christine Ferry, Samia Gaouar, Benoit Fischer, Marcel Boeglin, Nicodème Paul, et al.. Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108 (51), pp.20603-20608. ⟨10.1073/pnas.1102572108⟩. ⟨hal-04143715⟩