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The AF-1 and AF-2 Domains of RARγ2 and RXRα Cooperate for Triggering the Transactivation and the Degradation of RARγ2/RXRα Heterodimers
In eukaryotic cells, liganded RARγ2/RXRα heterodimers activate the transcription of retinoic acid (RA) target genes and then are degraded through the ubiquitin-proteasome pathway. In this study, we dissected the role of the RARγ2 and RXRα partners as well as of their respective AF-1 and AF-2 dom...
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Published in: | The Journal of biological chemistry 2003-09, Vol.278 (36), p.34458 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | In eukaryotic cells, liganded RARγ2/RXRα heterodimers activate
the transcription of retinoic acid (RA) target genes and then are degraded
through the ubiquitin-proteasome pathway. In this study, we dissected the role
of the RARγ2 and RXRα partners as well as of their respective AF-1
and AF-2 domains in the processes of transactivation and degradation.
RARγ2 is the âengineâ initiating transcription and its own
degradation subsequent to ligand binding. Integrity of its AF-2 domain and
phosphorylation of its AF-1 domain are required for both the degradation and
the transactivation of the receptor. Deletion of the whole AF-1 domain does
not impair these processes but shifts the receptor toward other proteolytic
pathways through RXRα. In contrast, RXRα plays only a modulatory
role, cooperating with RARγ2 through its AF-2 domain and its
phosphorylated AF-1 domain in both the transcription activity and the
degradation of the RARγ2/RXRα heterodimers. Our results underline
that the AF-1 and AF-2 domains of each heterodimer partner cooperate with one
other and that this cooperation is relevant for both the transcription and
degradation processes. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M304952200 |