Gene interactions and pathways from curated databases and text-mining
EMBO J 2006, PMID: 16456540

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

Giannì, Maurizio; Parrella, Edoardo; Raska, Ivan; Gaillard, Emilie; Nigro, Elisa Agnese; Gaudon, Claudine; Garattini, Enrico; Rochette-Egly, Cécile

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.

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Text Mining Data

RARalpha → SRC-3: " 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 "

Manually curated Databases

  • IRef Biogrid Interaction: ATF2 — MAPK14 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: RARA — NCOA3 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: MAPK1 — NCOA3 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: NCOA3 — MAPK14 (direct interaction, enzymatic study)
  • IRef Hprd Interaction: RARA — NCOA3 (in vivo)
  • IRef Hprd Interaction: RARA — NCOA3 (two hybrid)
  • IRef Hprd Interaction: RARA — NCOA3 (in vitro)
  • IRef Hprd Interaction: RELA — NCOA3 (in vivo)
  • IRef Hprd Interaction: RARG — NCOA3 (two hybrid)
  • IRef Hprd Interaction: RARG — NCOA3 (in vitro)
  • IRef Hprd Interaction: RARG — NCOA3 (in vivo)
  • IRef Hprd Interaction: RARA — NCOA1 (in vitro)
  • IRef Hprd Interaction: RARA — NCOA1 (two hybrid)
  • IRef Intact Interaction: NCOA1 — RARA (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: NCOA3 — RARA (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: NCOA3 — RELA (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: NCOA3 — MAPK14 (phosphorylation reaction, protein kinase assay)
In total, 7 gene pairs are associated to this article in curated databases