Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RARγ degradation and transactivation

Maurizio Giannì, Annie Bauer, Enrico Garattini, Pierre Chambon, Cécile Rochette-Egly

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

The nuclear retinoic acid receptor RARγ2 undergoes proteasome-dependent degradation upon ligand binding. Here we provide evidence that the domains that signal proteasome-mediated degradation overlap with those that activate transcription, i.e. the activation domains AF-1 and AF-2. The AF-1 domain signals RARγ2 degradation through its phosphorylation by p38MAPK in response to RA. The AF-2 domain acts via the recruitment of SUG-1, which belongs to the 19S regulatory subunit of the 26S proteasome. Blocking RARγ2 degradation through inhibition of either the p38MAPK pathway or the 26S proteasome function impairs its RA-induced transactivation activity. Thus, the turnover of RARγ2 is linked to transactivation.

Original languageEnglish
Pages (from-to)3760-3769
Number of pages10
JournalEMBO Journal
Volume21
Issue number14
DOIs
Publication statusPublished - Jul 15 2002

Fingerprint

Phosphorylation
Furylfuramide
Transcriptional Activation
Proteasome Endopeptidase Complex
Degradation
Retinoic Acid Receptors
Transcription
Ligands
Chemical activation
ATP dependent 26S protease

Keywords

  • Degradation
  • p38MAPK
  • Phosphorylation
  • Proteasome
  • RARγ
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RARγ degradation and transactivation. / Giannì, Maurizio; Bauer, Annie; Garattini, Enrico; Chambon, Pierre; Rochette-Egly, Cécile.

In: EMBO Journal, Vol. 21, No. 14, 15.07.2002, p. 3760-3769.

Research output: Contribution to journalArticle

Giannì, Maurizio ; Bauer, Annie ; Garattini, Enrico ; Chambon, Pierre ; Rochette-Egly, Cécile. / Phosphorylation by p38MAPK and recruitment of SUG-1 are required for RA-induced RARγ degradation and transactivation. In: EMBO Journal. 2002 ; Vol. 21, No. 14. pp. 3760-3769.
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