Nucleic Acids Research Advance Access originally published online on May 8, 2009
Nucleic Acids Research 2009 37(12):4100-4115; doi:10.1093/nar/gkp333
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2009, Vol. 37, No. 12 4100-4115
© 2009 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Molecular characterization of SMILE as a novel corepressor of nuclear receptors
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, 500-757, Republic of Korea
*To whom correspondence should be addressed. Tel: +82 62 530 0503; Fax: +82 62 530 0506. Email: hsc{at}chonnam.ac.kr
Received March 25, 2009. Revised April 20, 2009. Accepted April 20, 2009.
SMILE (small heterodimer partner interacting leucine zipper protein) has been identified as a coregulator in ER signaling. In this study, we have examined the effects of SMILE on other NRs (nuclear receptors). SMILE inhibits GR, CAR and HNF4
-mediated transactivation. Knockdown of SMILE gene expression increases the transactivation of the NRs. SMILE interacts with GR, CAR and HNF4 in vitro and in vivo. SMILE and these NRs colocalize in the nucleus. SMILE binds to the ligand-binding domain or AF2 domain of the NRs. Competitions between SMILE and the coactivators GRIP1 or PGC-1 have been demonstrated in vitro and in vivo. Furthermore, an intrinsic repressive activity of SMILE is observed in Gal4-fusion system, and the intrinsic repressive domain is mapped to the C-terminus of SMILE, spanning residues 203–354. Moreover, SMILE interacts with specific HDACs (histone deacetylases) and SMILE-mediated repression is released by HDAC inhibitor trichostatin A, in a NR-specific manner. Finally, ChIP (chromatin immunoprecipitation) assays reveal that SMILE associates with the NRs on the target gene promoters. Adenoviral overexpression of SMILE represses GR-, CAR- and HNF4-mediated target gene expression. Overall, these results suggest that SMILE functions as a novel corepressor of NRs via competition with coactivators and the recruitment of HDACs.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y.-B. Xie, J.-H. Park, D.-K. Kim, J. H. Hwang, S. Oh, S. B. Park, M. Shong, I.-K. Lee, and H.-S. Choi Transcriptional Corepressor SMILE Recruits SIRT1 to Inhibit Nuclear Receptor Estrogen Receptor-related Receptor {gamma} Transactivation J. Biol. Chem., October 16, 2009; 284(42): 28762 - 28774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chanda, T. Li, K.-H. Song, Y.-H. Kim, J. Sim, C. H. Lee, J. Y. L. Chiang, and H.-S. Choi Hepatocyte Growth Factor Family Negatively Regulates Hepatic Gluconeogenesis via Induction of Orphan Nuclear Receptor Small Heterodimer Partner in Primary Hepatocytes J. Biol. Chem., October 16, 2009; 284(42): 28510 - 28521. [Abstract] [Full Text] [PDF]
|
|