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525882 
Journal Article 
SMRT recruitment by PPAR gamma is mediated by specific residues located in its carboxy-terminal interacting domain (vol 259, pg 43, 2006) 
Sutanto, MM; Symons, MS; Cohen, RN 
2007 
1 
Molecular and Cellular Endocrinology
ISSN: 0303-7207
EISSN: 1872-8057 
267 
1-2 
137-143 
English 
The silencing mediator of retinoid and thyroid hormone receptors (SMRT) has been shown to play an important role in adipogenesis and PPAR gamma transcriptional activity. SMRT contains two interacting domains that mediate interactions with nuclear receptors. Interestingly, SMRT is recruited to PPAR gamma via its C-terminal interacting domain, and mutation of the proximal interacting domain does not interfere with recruitment via PPAR gamma. To understand how the distal interacting domain mediates recruitment by PPAR gamma, we have now mutated residues in this domain to the corresponding amino acids found in the proximal domain. We show that specific residues in this distal domain are vital for interactions with PPAR gamma, but not for a related receptor, RAR alpha. Furthermore, naturally occurring SMRT isoforms that differ in interacting domain sequences have different effects on PPAR gamma as opposed to RARa recruitment. These data suggest that PPAR gamma and RAR alpha interact with SMRT via distinct mechanisms. These differences will be important as ligands are designed that lead to specific patterns of nuclear receptor recruitment of corepressors. Published by Elsevier Ireland Ltd. 
nuclear hormone-receptors; transcriptional activity; insulin-resistance; co-repressor; corepressors; ligand