Article Dans Une Revue EMBO Journal Année : 2006

P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARalpha-mediated transcription.

Maurizio Giannì
  • Fonction : Auteur
Edoardo Parrella
  • Fonction : Auteur
Ivan Raska
  • Fonction : Auteur
Emilie Gaillard
  • Fonction : Auteur
Elisa Agnese Nigro
  • Fonction : Auteur
Enrico Garattini
  • Fonction : Auteur

Résumé

Nuclear retinoic acid (RA) receptors (RARs) activate gene expression through dynamic interactions with coregulators in coordination with the ligand and phosphorylation processes. Here we show that during RA-dependent activation of the RARalpha isotype, the p160 coactivator pCIP/ACTR/AIB-1/RAC-3/TRAM-1/SRC-3 is phosphorylated by p38MAPK. SRC-3 phosphorylation has been correlated to an initial facilitation of RARalpha-target genes activation, via the control of the dynamics of the interactions of the coactivator with RARalpha. Then, phosphorylation inhibits transcription via promoting the degradation of SRC-3. In line with this, inhibition of p38MAPK markedly enhances RARalpha-mediated transcription and RA-dependent induction of cell differentiation. SRC-3 phosphorylation and degradation occur only within the context of RARalpha complexes, suggesting that the RAR isotype defines a phosphorylation code through dictating the accessibility of the coactivator to p38MAPK. We propose a model in which RARalpha transcriptional activity is regulated by SRC-3 through coordinated events that are fine-tuned by RA and p38MAPK.

Dates et versions

hal-00187931 , version 1 (15-11-2007)

Identifiants

Citer

Maurizio Giannì, Edoardo Parrella, Ivan Raska, Emilie Gaillard, Elisa Agnese Nigro, et al.. P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARalpha-mediated transcription.. EMBO Journal, 2006, 25 (4), pp.739-51. ⟨10.1038/sj.emboj.7600981⟩. ⟨hal-00187931⟩
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