Molecular Biology of the Cell Call for Nominations: MBC Editor-in-Chief

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E02-07-0375 on December 7, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E02-07-0375v1
14/3/1279    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chou, W.-C.
Right arrow Articles by Kardassis, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chou, W.-C.
Right arrow Articles by Kardassis, D.

Vol. 14, Issue 3, 1279-1294, March 2003

Mechanism of a Transcriptional Cross Talk between Transforming Growth Factor-beta -regulated Smad3 and Smad4 Proteins and Orphan Nuclear Receptor Hepatocyte Nuclear Factor-4

Wan-Chih Chou,* Vassiliki Prokova,* Keiko Shiraishi,dagger Ulrich Valcourt,dagger Aristidis Moustakas,dagger Margarita Hadzopoulou-Cladaras,Dagger Vassilis I. Zannis,* and Dimitris Kardassis*§

 *Department of Basic Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology of Hellas, Heraklion GR-71110, Greece;  dagger Ludwig Institute for Cancer Research, S-751 24 Uppsala, Sweden; and  Dagger Department of Biology, Section of Genetics, Development, and Molecular Biology, Aristotelian University of Thessaloniki, Thessaloniki GR-54124, Greece

We have shown previously that the transforming growth factor-beta (TGFbeta )-regulated Sma-Mad (Smad) protein 3 and Smad4 proteins transactivate the apolipoprotein C-III promoter in hepatic cells via a hormone response element that binds the nuclear receptor hepatocyte nuclear factor 4 (HNF-4). In the present study, we show that Smad3 and Smad4 but not Smad2 physically interact with HNF-4 via their Mad homology 1 domains both in vitro and in vivo. The synergistic transactivation of target promoters by Smads and HNF-4 was shown to depend on the specific promoter context and did not require an intact beta -hairpin/DNA binding domain of the Smads. Using glutathione S-transferase interaction assays, we established that two regions of HNF-4, the N-terminal activation function 1 (AF-1) domain (aa 1-24) and the C-terminal F domain (aa 388-455) can mediate physical Smad3/HNF-4 interactions in vitro. In vivo, Smad3 and Smad4 proteins enhanced the transactivation function of various GAL4-HNF-4 fusion proteins via the AF-1 and the adjacent DNA binding domain, whereas a single tyrosine to alanine substitution in AF-1 abolished coactivation by Smads. The findings suggest that the transcriptional cross talk between the TGFbeta -regulated Smads and HNF-4 is mediated by specific functional domains in the two types of transcription factors. Furthermore, the specificity of this interaction for certain target promoters may play an important role in various hepatocyte functions, which are regulated by TGFbeta and the Smads.

§ Corresponding author. E-mail address: kardasis{at}imbb.forth.gr.

Molecular Biology of the Cell
Vol. 14, 1279-1294, March 2003
Copyright © 2003 by The American Society for Cell Biology


This article has been cited by other articles:


Home page
 DiabetesHome page
L. W. Harries, J. M. Locke, B. Shields, N. A. Hanley, K. P. Hanley, A. Steele, P. R. Njolstad, S. Ellard, and A. T. Hattersley
The Diabetic Phenotype in HNF4A Mutation Carriers Is Moderated By the Expression of HNF4A Isoforms From the P1 Promoter During Fetal Development
Diabetes, June 1, 2008; 57(6): 1745 - 1752.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
P. Dai, T. Nakagami, H. Tanaka, T. Hitomi, and T. Takamatsu
Cx43 Mediates TGF-beta Signaling through Competitive Smads Binding to Microtubules
Mol. Biol. Cell, June 1, 2007; 18(6): 2264 - 2273.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
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]

Home page
 Pharmacol. Rev.Home page
G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al.
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Karl, M. Berho, J. Pignac-Kobinger, G. E. Striker, and S. J. Elliot
Differential Effects of Continuous and Intermittent 17{beta}-Estradiol Replacement and Tamoxifen Therapy on the Prevention of Glomerulosclerosis: Modulation of the Mesangial Cell Phenotype in Vivo
Am. J. Pathol., August 1, 2006; 169(2): 351 - 361.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
G. Li, J. H. Heaton, and T. D. Gelehrter
Role of Steroid Receptor Coactivators in Glucocorticoid and Transforming Growth Factor {beta} Regulation of Plasminogen Activator Inhibitor Gene Expression
Mol. Endocrinol., May 1, 2006; 20(5): 1025 - 1034.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Jinnin, H. Ihn, and K. Tamaki
Characterization of SIS3, a Novel Specific Inhibitor of Smad3, and Its Effect on Transforming Growth Factor-beta1-Induced Extracellular Matrix Expression
Mol. Pharmacol., February 1, 2006; 69(2): 597 - 607.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
N. R. Dunn, C. H. Koonce, D. C. Anderson, A. Islam, E. K. Bikoff, and E. J. Robertson
Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile
Genes & Dev., January 1, 2005; 19(1): 152 - 163.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Briancon, A. Bailly, F. Clotman, P. Jacquemin, F. P. Lemaigre, and M. C. Weiss
Expression of the {alpha}7 Isoform of Hepatocyte Nuclear Factor (HNF) 4 Is Activated by HNF6/OC-2 and HNF1 and Repressed by HNF4{alpha}1 in the Liver
J. Biol. Chem., August 6, 2004; 279(32): 33398 - 33408.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Aggelidou, P. Iordanidou, P. Tsantili, G. Papadopoulos, and M. Hadzopoulou-Cladaras
Critical Role of Residues Defining the Ligand Binding Pocket in Hepatocyte Nuclear Factor-4{alpha}
J. Biol. Chem., July 16, 2004; 279(29): 30680 - 30688.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Ohshima and K. Shimotohno
Transforming Growth Factor-{beta}-mediated Signaling via the p38 MAP Kinase Pathway Activates Smad-dependent Transcription through SUMO-1 Modification of Smad4
J. Biol. Chem., December 19, 2003; 278(51): 50833 - 50842.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Eeckhoute, B. Oxombre, P. Formstecher, P. Lefebvre, and B. Laine
Critical role of charged residues in helix 7 of the ligand binding domain in Hepatocyte Nuclear Factor 4{alpha} dimerisation and transcriptional activity
Nucleic Acids Res., November 15, 2003; 31(22): 6640 - 6650.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Li, S. Wang, and T. D. Gelehrter
Identification of Glucocorticoid Receptor Domains Involved in Transrepression of Transforming Growth Factor-{beta} Action
J. Biol. Chem., October 24, 2003; 278(43): 41779 - 41788.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]