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

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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.