ArticleMolecular biology of the cell2003
Mechanism of a transcriptional cross talk between transforming growth factor-beta-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- Sildenafil Inhibits the Growth and Epithelial-to-mesenchymal Transition of Cervical Cancer via the TGF-β1/Smad2/3 Pathway.Current cancer drug targets · 2023Article
- TGF-β Family Signaling in Ductal Differentiation and Branching Morphogenesis.Cold Spring Harbor perspectives in biology · 2018Review
- Hepatocyte Nuclear Factor 4 Alpha Promotes Definitive Endoderm Differentiation from Human Induced Pluripotent Stem Cells.Stem cell reviews and reports · 2017Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Article
- Fn14, a Downstream Target of the TGF-β Signaling Pathway, Regulates Fibroblast Activation.PloS one · 2015Article
- Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells.The Journal of biological chemistry · 2011Article
- Global gene expression responses to low- or high-dose radiation in a human three-dimensional tissue model.Radiation research · 2011Article
- Article
- Nuclear hormone receptors in diabetic nephropathy.Nature reviews. Nephrology · 2010Review
- An integrative ChIP-chip and gene expression profiling to model SMAD regulatory modules.BMC systems biology · 2009Article
- Hepatocyte nuclear factor 4alpha regulation of bile acid and drug metabolism.Expert opinion on drug metabolism & toxicology · 2009Review
- Cx43 mediates TGF-beta signaling through competitive Smads binding to microtubules.Molecular biology of the cell · 2007Article
- Inhibition of hepatocyte nuclear factor 4 transcriptional activity by the nuclear factor kappaB pathway.The Biochemical journal · 2006Article
- Differential effects of continuous and intermittent 17beta-estradiol replacement and tamoxifen therapy on the prevention of glomerulosclerosis: modulation of the mesangial cell phenotype in vivo.The American journal of pathology · 2006Article
- Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo.Developmental biology · 2006Article
- Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile.Genes & development · 2005Article
- Critical role of charged residues in helix 7 of the ligand binding domain in Hepatocyte Nuclear Factor 4alpha dimerisation and transcriptional activity.Nucleic acids research · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.