"The structure of the S4AF trimer reveals novel features important for Smad4 function."

"A tandem sulfate-ion-binding site was identified within the subunit interface, which may interact with the phosphorylated C-terminal sequence of pathway-restricted SMAD proteins."

"endogenous or even transfected Smad3 cannot bind to the SBE in the absence of Smad4."

"Exposure of HUVECs to hypoxia resulted in phosphorylation and nuclear transportation of Smad2 and Smad3 proteins as well as stimulation of transcriptional activities of Smad3 and the transcription factor hypoxia-inducible factor-1alpha and culminated in up-regulation of TGF-beta2 gene expression."

"EID-2 interacts constitutively with Smad proteins, and most strongly with Smad3."

"Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies."

"A protein-protein interaction between Smad3 and Smad4 with hZimp10 was identified in glutathione S-transferase-pulldown and co-immunoprecipitation assays."

"BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent."

"We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm."

"This was associated with the regulation by miR-125 of SMAD4, a key regulator of pluripotent stem cell lineage commitment."

"Overexpression of miR-199a significantly inhibited the ability of TGF-β to induce gastric cancer cell growth arrest and apoptosis in vitro, and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis."

"Tcf transcriptional activity was decreased to 70% in Dkk-3- or/and SMAD4-transfected PC-3 cells compared with control, indicating that Dkk-3 and SMAD4 inhibits the β-catenin-depending pathway in PC cells (Figure 7D).Effect of miR-183 on Wnt-β-catenin pathwayAs TOPflash luciferase activity was significantly decreased with Dkk-3 and SMAD4 overexpression, we also performed the same assay using miR-183 inhibitor."

"knockdown of Smad4 reduced the levels of ECM in HTMCs."

"knocked down SMAD4 could partially reverse TGF-β-induced migration, invasion, and EMT progression in the ESCC cell line EC-1."

"Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes."

"the full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 µM (Fig."

"The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6–1.2 µM concentration range"

"TGF-β, Nodal, and Activin receptors phosphorylate SMAD2 and SMAD3."

"hMAD-3 and -4 synergized to induce strong ligand-independent TGF-beta-like responses."

"Smad6 interacted with all species tested (Smad1, Smad2, and Smad4), whereas Smad7 interacted only with Smad6 (Fig."

"Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter."

"Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells."

"Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription."

"SMAD4, is absolutely required for normal FSH synthesis in both male and female mice."

"the Runx2- and Smad4-specific siRNAs inhibited the expression of Runx2 and Smad4 at the level of messenger RNA and protein."

"Wnt1cre;Sm4c/n;TgEng loxP embryos demonstrated characteristic defects in the outflow tract, persistent truncus arteriosus, in which there was a loss of septation of the aorta and pulmonary trunk which form the outflow tract ( Fig."

"Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions."

"Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects."

"the deletion of Smad4 in cardiomyocytes resulted in cardiac hypertrophy characterized by an increase in the size of cardiac myocytes, age-associated fibrosis, and reexpression of certain fetal genes."

"phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and mitogen-activated protein kinase-ERK (MEK) 1 were increased in the Smad4 mutants, suggesting that an upregulation of MEK1-ERK1/2 signaling as a consequence of deletion of Smad4 underlies the impaired cardiac function."

"Each collagen also bound to the MH2 domains of Smads 4 and 7 and, to a lesser extent, full-length Smads 1, 2, 3, and 4."

"a Cre-loxP-mediated liver-specific disruption of SMAD4 results in markedly decreased hepcidin expression and accumulation of iron in many organs, which is most pronounced in liver, kidney, and pancreas."

"transcriptional activation of hepcidin is abrogated in SMAD4-deficient hepatocytes in response to iron overload, TGF-beta, BMP, or IL-6."

"Smad4 deficiency blocked the aggregation of Sox9-positive progenitors, thereby preventing chondrogenic differentiation as revealed by absence of collagen type II."

"removal of Smad4 in nephrogenic mesenchyme using the Bmp7(cre/+) allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction."

"inhibition of SMAD4 synthesis using SMAD4 antisense oligonucleotides reduced the number of apoptotic cells under stimulation with SNAP from 13.3 +/- 1.2% to control levels (8 +/- 1%, p < 0.05, n = 6)."

"Our paper is the first to show that the Smad2,4/LEF1 complex replaces beta-catenin/LEF1 during activation of EMT in vivo by TGFbeta3."

"silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs."

"the elements of the activin signaling pathway are present, intact, and functional."

"Following cleavage, there is enhanced recruitment of Smad3/4 to a C-terminal FLNa fragment with nuclear translocation and subsequent binding to the promoter region of the laminin gamma1 (lamc1) gene."

"hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE)."

"The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand."

"Both Smad3 and Smad4 were required for the interaction with beta-catenin and protected beta-catenin from an ubiquitin-proteasome-dependent degradation."

"reduced binding of the transcriptional coactivator CREB-binding protein 1 to transcriptional complexes containing Smad2, Smad3, and Smad4."

"adenoviral-mediated expression of dominant negative Smad4 blocked the ability of TGF-beta to activate acinar cell MAP kinase, demonstrating that this activation is downstream of Smads."

"the sumolyation (SUMO2/3) of Smad4 was enhanced significantly in the high glucose groups compared with the control group (P < 0.05)."

"MiR-29a was directly up-regulated by TGF-β/Smad4 signaling in human and mice endothelial cells."

"Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD"

"myocardial Smad4 conditional knockout fetuses exhibited cardiac defects, including double-outlet right ventricle (DORV) (Fig. 4D,H), ventricular septal defect (VSD) (Fig. 4D,H), decreased density of trabeculae in the ventricles and thinning of the compact layer of the ventricular myocardium (Fig. 4B,D,H,F)."