This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yeo, M. G. Articles by Lee, M.-O. Search for Related Content PubMed PubMed Citation Articles by Yeo, M. G. Articles by Lee, M.-O. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Medline Plus Health Information Liver Cancer

Negative Cross-Talk between Nur77 and Small Heterodimer Partner and Its Role in Apoptotic Cell Death of Hepatoma Cells

College of Pharmacy (M.G.Y., Y.-G.Y., M.-O.L.), Seoul National University, Seoul 151-742, Korea; Hormone Research Center (H.-S.C.), School of Biological Sciences and Technology, Chonnam National University, Kwangju 138-736, Korea; and Asan Institute for Life Science (Y.K.P.), University of Ulsan College of Medicine, Seoul 500-757, Korea

Address all correspondence and requests for reprints to: Mi-Ock Lee, Ph.D., College of Pharmacy, Seoul National University, San 56-1 Sillim, Kwanak, Seoul 151-742, Korea. E-mail: molee{at}snu.ac.kr.

Nur77, an orphan nuclear receptor, has been implicated in apoptosis of a variety of cell types, including hepatocytes. The small heterodimer partner (SHP) binds and inhibits the function of many nuclear receptors. Here, we investigated cross-talk between Nur77 and SHP during anti-Fas antibody (CH11)-mediated apoptosis of hepatic cells. Expression of SHP decreased, whereas antisense SHP enhanced, the transcriptional activity of Nur77 in HepG2 cells. SHP and Nur77 were physically associated in vivo and colocalized in the nucleus. SHP decreased the transactivation function of the N-terminal domain of Nur77 that recruits coactivators. Nur77 and SHP competitively bound to cAMP response element-binding protein-binding protein and the expression of coactivators, such as cAMP response element-binding protein-binding protein and activating signal cointegrator-2, recovered the decreased function of Nur77 caused by SHP. Finally, SHP was differentially expressed in hepatoma cell lines in that it was not detected in the interferon- (IFN)/CH11-sensitive SNU354, whereas it was significantly expressed in the IFN/CH11-resistant HepG2. Interestingly, a stable SNU354 cell line that expressed SHP became resistant to the IFN/CH11-induced apoptosis. Together, our results suggest that SHP plays a key role in the regulation of Nur77 activation and thereby in Nur77-mediated apoptosis in the liver.

NURSA Molecule Pages Link:

Nuclear Receptors:   SHP  |  NGFIB  |  NURR1  |  NOR1

Coregulators:   PGC-1  |  CBP  |  p300  |  ASC-2

This article has been cited by other articles:

				Y. D. Kim, K.-G. Park, Y.-S. Lee, Y.-Y. Park, D.-K. Kim, B. Nedumaran, W. G. Jang, W.-J. Cho, J. Ha, I.-K. Lee, et al. Metformin Inhibits Hepatic Gluconeogenesis Through AMP-Activated Protein Kinase-Dependent Regulation of the Orphan Nuclear Receptor SHP Diabetes, February 1, 2008; 57(2): 306 - 314. [Abstract] [Full Text] [PDF]

				H. Dong, C. L. Yauk, A. Williams, A. Lee, G. R. Douglas, and M. G. Wade Hepatic Gene Expression Changes in Hypothyroid Juvenile Mice: Characterization of a Novel Negative Thyroid-Responsive Element Endocrinology, August 1, 2007; 148(8): 3932 - 3940. [Abstract] [Full Text] [PDF]

				L. Farhana, M. I. Dawson, M. Leid, L. Wang, D. D. Moore, G. Liu, Z. Xia, and J. A. Fontana Adamantyl-Substituted Retinoid-Related Molecules Bind Small Heterodimer Partner and Modulate the Sin3A Repressor Cancer Res., January 1, 2007; 67(1): 318 - 325. [Abstract] [Full Text] [PDF]

				B. Liu, J.-f. Wu, Y.-y. Zhan, H.-z. Chen, X.-y. Zhang, and Q. Wu Regulation of the Orphan Receptor TR3 Nuclear Functions by c-Jun N Terminal Kinase Phosphorylation Endocrinology, January 1, 2007; 148(1): 34 - 44. [Abstract] [Full Text] [PDF]

				J. H. Suh, J. Huang, Y.-Y. Park, H.-A Seong, D. Kim, M. Shong, H. Ha, I.-K. Lee, K. Lee, L. Wang, et al. Orphan Nuclear Receptor Small Heterodimer Partner Inhibits Transforming Growth Factor-beta Signaling by Repressing SMAD3 Transactivation J. Biol. Chem., December 22, 2006; 281(51): 39169 - 39178. [Abstract] [Full Text] [PDF]

				A. K. Iyer, Y.-H. Zhang, and E. R. B. McCabe Dosage-Sensitive Sex Reversal Adrenal Hypoplasia Congenita Critical Region on the X Chromosome, Gene 1 (DAX1) (NR0B1) and Small Heterodimer Partner (SHP) (NR0B2) Form Homodimers Individually, as Well as DAX1-SHP Heterodimers Mol. Endocrinol., October 1, 2006; 20(10): 2326 - 2342. [Abstract] [Full Text] [PDF]