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.
Free PMC Article
Cullin 3 mediates SRC-3 ubiquitination and degradation to control the retinoic acid response
Riferimento:
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20603-8.
Autori:
Ferry C, Gaouar S, Fischer B, Boeglin M, Paul N, Samarut E, Piskunov A, Pankotai-Bodo G, Brino L, Rochette-Egly C.
Fonte:
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20603-8.
Anno:
2011
Azione:
SRC-3 è un importante coattivatore di recettori nucleari, compreso il recettore α dell'acido retinoico (RA), partecipando all'effetto antiproliferativo di RA.
Target:
RC-3-RA/effetto antiproliferativo.
Sostanze: