SUG-1 plays proteolytic and non-proteolytic roles in the control of retinoic acid target genes via its interaction with SRC-3. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2009

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

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Abstract

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.

Dates and versions

inserm-00383334 , version 1 (12-05-2009)

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Christine Ferry, Maurizio Gianni, Sébastien Lalevée, Nathalie Bruck, Jean-Luc Plassat, et al.. SUG-1 plays proteolytic and non-proteolytic roles in the control of retinoic acid target genes via its interaction with SRC-3.. Journal of Biological Chemistry, 2009, 284 (12), pp.8127-35. ⟨10.1074/jbc.M808815200⟩. ⟨inserm-00383334⟩
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