SUG-1 plays proteolytic and non-proteolytic roles in the control of retinoic acid target genes via its interaction with SRC-3.

Nuclear retinoic acid receptor alpha (RARalpha) activates gene expression through dynamic interactions with coregulatory protein complexes, the assembly of which is directed by the ligand and the AF-2 domain of RARalpha. Then RARalpha and its coactivator SRC-3 are degraded by the proteasome. Recently it has emerged that the proteasome also ...
plays a key role in RARalpha-mediated transcription. Here we show that SUG-1, one of the six ATPases of the 19 S regulatory complex of the 26 S proteasome, interacts with SRC-3, is recruited at the promoters of retinoic acid (RA) target genes, and thereby participates to their transcription. In addition, SUG-1 also mediates the proteasomal degradation of SRC-3. However, when present in excess amounts, SUG-1 blocks the activation of RARalpha target genes and the degradation of RARalpha that occurs in response to RA, via its ability to interfere with the recruitment of SRC-3 and other coregulators at the AF-2 domain of RARalpha. We propose a model in which the ratio between SUG-1 and SRC-3 is crucial for the control of RARalpha functioning. This study provides new insights into how SUG-1 has a unique role in linking the transcription and degradation processes via its ability to interact with SRC-3.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, COS Cells, Cercopithecus aethiops, Gene Expression Regulation, HeLa Cells, Histone Acetyltransferases, Humans, LIM Domain Proteins, Models, Biological, Nuclear Receptor Coactivator 3, Proteasome Endopeptidase Complex, Protein Structure, Tertiary, Receptors, Retinoic Acid, Trans-Activators, Transcription Factors, Transcription, Genetic, Tretinoin
J. Biol. Chem.
Date: Mar. 20, 2009
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