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

ABSTRACT: The nuclear retinoic acid receptor RAR gamma 2 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 RAR gamma 2 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 RAR gamma 2 degradation through inhibition of either the p38MAPK pathway or the 26S proteasome function impairs its RA-induced transactivation activity. Thus, the turnover of RAR gamma 2 is linked to transactivation.

SUBMITTER: Gianni M

PROVIDER: S-EPMC126119 | biostudies-literature | 2002 Jul

REPOSITORIES: biostudies-literature

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

Giannì Maurizio M Bauer Annie A Garattini Enrico E Chambon Pierre P Rochette-Egly Cécile C

The EMBO journal 20020701 14

The nuclear retinoic acid receptor RAR gamma 2 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 RAR gamma 2 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 ...[more]

PMID: 12110588

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