| + |
SKI | down-regulates activity 
binding
|
SMAD2/SMAD4 |
0.787 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253300 |
|
|
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 12793438 |
The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
SMAD2/SMAD4 | up-regulates quantity by expression 
transcriptional regulation
|
NANOG |
0.574 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-242044 |
|
|
Homo sapiens |
Esophageal Squamous Cell Carcinoma Cell |
| pmid |
sentence |
| 18682241 |
We also find that SMADs bind with the NANOG promoter and that SMAD2/3 activity enhances NANOG promoter activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-242049 |
|
|
Homo sapiens |
Embryonic Stem Cell |
| pmid |
sentence |
| 19279133 |
Here, we show that Smad2/3, the downstream effectors of Activin/Nodal signalling, bind and directly control the activity of the Nanog gene in hESCs. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
SMAD2/SMAD4 | up-regulates activity
binding
|
SP1 |
0.617 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256288 |
|
|
Homo sapiens |
HaCaT Cell |
| pmid |
sentence |
| 11013220 |
TGF-β induces the formation and nuclear translocation of a trimeric Smad complex, which in this case is likely to consist of one monomer each of Smad2, Smad3 and Smad4. Smad2 and Smad4 associate directly with Sp1 and co-activate the transcriptional activity of Sp1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD2/SMAD4 | up-regulates 
|
M2_polarization |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249550 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22703233 |
Our results establish a novel biological role for TGFbeta signaling in controlling expression of genes characteristic for alternatively activated macrophages. We speculate that lack of TbetaRII signaling reduces the anti-inflammatory M2 phenotype of macrophages because of reduced expression of these products. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253588 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27418133 |
The SMAD2/3 and PI3K/AKT signaling pathways were crucial for TGF-?-induced SNAIL overexpression in THP-1 cells. These findings suggest that TGF-? skews macrophage polarization towards a M2-like phenotype via SNAIL up-regulation, and blockade of TGF-?/SNAIL signaling restores the production of pro-inflammatory cytokines |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Multiple sclerosis |
| + |
SKIL | down-regulates activity
binding
|
SMAD2/SMAD4 |
0.85 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253302 |
|
|
Homo sapiens |
Melanoma Cell |
| pmid |
sentence |
| 12793438 |
The ski and snon protein family associate with and repress the activity of smad2, smad3, and smad4, three members of the tgf-fl signaling pathway |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
SMAD2/SMAD4 | up-regulates activity
binding
|
AP1 |
0.533 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256180 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22926518 |
The activated TGFβ type I receptor kinase propagates the signal within the cell through phosphorylation of the receptor-regulated (R-)Smad proteins Smad2 and Smad3 at their extreme carboxyl-terminal serine residues.1, 2 The activated R-Smads then form heteromeric complexes with the common-partner (Co-)Smad, Smad4, and accumulate in the nucleus, where they can bind DNA and regulate gene expression. The Smads control gene expression in a cell type-specific manner by interacting with other proteins, such as AP-1, AP-2 and Ets transcription factors and specific co-activators and co-repressors. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
SMAD2/SMAD4 | up-regulates quantity by expression
transcriptional regulation
|
CDKN2B |
0.622 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256287 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11013220 |
Our data demonstrate the physical interactions and functional cooperativity of Sp1 with a complex of Smad2, Smad3 and Smad4 in the induction of the p15Ink4B gene. These findings explain the tumor suppressor roles of Smad2 and Smad4 in growth arrest signaling by TGF-β. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
SMAD2/SMAD4 | up-regulates
|
Fibrosis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260440 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30017632 |
Smad4 interacted withSmad2/3 and participated in the transcription of downstream pro-fi-brotic target genes |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | TGF-beta Signaling |
| + |
SMAD2/SMAD4 | up-regulates quantity by expression
transcriptional regulation
|
SNAI1 |
0.502 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281166 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 18832382 |
In the present study we investigated the molecular mechanisms by which HMGA2 induces EMT. We found that HMGA2 regulates expression of many important repressors of E-cadherin. Among these, we analyzed in detail the zinc-finger transcription factor SNAIL1, which plays key roles in tumor progression and EMT. We demonstrate that HMGA2 directly binds to the SNAIL1 promoter and acts as a transcriptional regulator of SNAIL1 expression. Furthermore, we observed that HMGA2 cooperates with the TGF-beta/Smad pathway in regulating SNAIL1 gene expression. The mechanism behind this cooperation involves physical interaction between these factors, leading to an increased binding of Smads to the SNAIL1 promoter |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMAD2 | form complex 
binding
|
SMAD2/SMAD4 |
0.727 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235188 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11274206 |
the receptor-regulated Smad, such as Smad2, forms a heterocomplex with the co-mediator Smad, Smad4 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
SMAD4 | form complex
binding
|
SMAD2/SMAD4 |
0.727 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-235178 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11274206 |
the receptor-regulated Smad, such as Smad2, forms a heterocomplex with the co-mediator Smad, Smad4 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Pancreatic ductal adenocarcinoma (PDA), TGF-beta Signaling, TGFb in cancer |
| + |
TGFb | up-regulates quantity by expression
transcriptional regulation
|
SMAD2/SMAD4 |
0.655 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281161 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30017632 |
Transforming growth factor-β1 (TGF-β1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic (Smad) signaling. Different TGF-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor, Multiple sclerosis, Pancreatic ductal adenocarcinoma (PDA), TGFb in cancer |
| + |
SMAD2/SMAD4 | down-regulates quantity by repression 
transcriptional regulation
|
MYC |
0.679 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256291 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11689553 |
To identify this pathway, we analyzed TGF-β-responsive elements in the human c-myc promoter and found that Smad proteins directly bound to an element in the c-myc promoter and suppressed c-myc promoter activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Hepatocellular Tumor |
| + |
SMAD2/SMAD4 | up-regulates activity
binding
|
HMGA2 |
0.535 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281162 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 18832382 |
In the present study we investigated the molecular mechanisms by which HMGA2 induces EMT. We found that HMGA2 regulates expression of many important repressors of E-cadherin. Among these, we analyzed in detail the zinc-finger transcription factor SNAIL1, which plays key roles in tumor progression and EMT. We demonstrate that HMGA2 directly binds to the SNAIL1 promoter and acts as a transcriptional regulator of SNAIL1 expression. Furthermore, we observed that HMGA2 cooperates with the TGF-beta/Smad pathway in regulating SNAIL1 gene expression. The mechanism behind this cooperation involves physical interaction between these factors, leading to an increased binding of Smads to the SNAIL1 promoter |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
SMAD2/SMAD4
CPX-3208