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 language | English |
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Pages (from-to) | 3760-3769 |
Number of pages | 10 |
Journal | EMBO Journal |
Volume | 21 |
Issue number | 14 |
DOIs | |
Publication status | Published - Jul 15 2002 |
Keywords
- Degradation
- p38MAPK
- Phosphorylation
- Proteasome
- RARγ
- Transcription
ASJC Scopus subject areas
- Genetics
- Cell Biology