| + |
ATM | up-regulates activity 
phosphorylation
|
ZEB1 |
0.477 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278329 |
Ser585 |
GDGNLSPsQPPLKNL |
Homo sapiens |
|
| pmid |
sentence |
| 25086746 |
Mechanistically, ATM kinase phosphorylates and stabilizes ZEB1 in response to DNA damage, and ZEB1 in turn directly interacts with USP7 and enhances its ability to deubiquitinate and stabilize CHK1, thereby promoting homologous recombination-dependent DNA repair and resistance to radiation.|Therefore, ATM dependent phosphorylation of ZEB1 at S585 is crucial for IR induced stabilization of ZEB1 but not the interaction between ZEB1 and USP7. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZEB1 | up-regulates quantity by expression
transcriptional regulation
|
VIM |
0.441 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281205 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 34638469 |
These signalling cascades are also implicated in the induction of EMT via the transcriptional control of EMT-associated transcription factors, such as SNAI1, TWIST, ZEB1, SLUG and TCF3 leading to vimentin expression, as described above (Figure 2). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZEB1 | down-regulates quantity by destabilization 
post transcriptional regulation
|
mir-205 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281212 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24627491 |
Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelial state with their expression lost in cells undergoing EMT. EMT can be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200 expression via a self-reinforcing double negative feedback loop to promote the mesenchymal state. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZEB1 | down-regulates quantity by destabilization
post transcriptional regulation
|
hsa-miR-200a-3p |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281213 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24627491 |
Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelial state with their expression lost in cells undergoing EMT. EMT can be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200 expression via a self-reinforcing double negative feedback loop to promote the mesenchymal state. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZEB1 | down-regulates quantity by destabilization
post transcriptional regulation
|
hsa-mir-200b-3p |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281214 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24627491 |
Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelial state with their expression lost in cells undergoing EMT. EMT can be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200 expression via a self-reinforcing double negative feedback loop to promote the mesenchymal state. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
mir-205 | down-regulates quantity by destabilization
post transcriptional regulation
|
ZEB1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281202 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18376396 |
On the basis of the preceding observations, we surmised that a function of miR-205 and the miR-200 family is to prevent expression of ZEB1 and SIP1 in epithelial cells, which may otherwise trigger EMT by downregulating E-cadherin, and further, that downregulation of the microRNAs may be sufficient to initiate EMT. To test this, we examined the effect of the microRNA inhibitors on cell phenotype.We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez.Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as δEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-miR-200a-3p | down-regulates quantity by destabilization
post transcriptional regulation
|
ZEB1 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281192 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18376396 |
On the basis of the preceding observations, we surmised that a function of miR-205 and the miR-200 family is to prevent expression of ZEB1 and SIP1 in epithelial cells, which may otherwise trigger EMT by downregulating E-cadherin, and further, that downregulation of the microRNAs may be sufficient to initiate EMT. To test this, we examined the effect of the microRNA inhibitors on cell phenotype.We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez.Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as δEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-mir-200b-3p | down-regulates quantity by destabilization
post transcriptional regulation
|
ZEB1 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281194 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18376396 |
On the basis of the preceding observations, we surmised that a function of miR-205 and the miR-200 family is to prevent expression of ZEB1 and SIP1 in epithelial cells, which may otherwise trigger EMT by downregulating E-cadherin, and further, that downregulation of the microRNAs may be sufficient to initiate EMT. To test this, we examined the effect of the microRNA inhibitors on cell phenotype.We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez.Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as δEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-miR-200c-3p | down-regulates quantity by destabilization
post transcriptional regulation
|
ZEB1 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281196 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18376396 |
On the basis of the preceding observations, we surmised that a function of miR-205 and the miR-200 family is to prevent expression of ZEB1 and SIP1 in epithelial cells, which may otherwise trigger EMT by downregulating E-cadherin, and further, that downregulation of the microRNAs may be sufficient to initiate EMT. To test this, we examined the effect of the microRNA inhibitors on cell phenotype.We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez.Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as δEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
hsa-miR-141-3p | down-regulates quantity by destabilization
post transcriptional regulation
|
ZEB1 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281198 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18376396 |
On the basis of the preceding observations, we surmised that a function of miR-205 and the miR-200 family is to prevent expression of ZEB1 and SIP1 in epithelial cells, which may otherwise trigger EMT by downregulating E-cadherin, and further, that downregulation of the microRNAs may be sufficient to initiate EMT. To test this, we examined the effect of the microRNA inhibitors on cell phenotype.We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez.Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as δEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SNAI1 | up-regulates quantity by expression
transcriptional regulation
|
ZEB1 |
0.325 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281168 |
|
|
Canidae |
95C Cell |
| pmid |
sentence |
| 18832382 |
We then analyzed the effect of Snail1 depletion on expression of the other four E-cadherin repressors, whose levels become increased by HMGA2 overexpression, Snail2, ZEB1, ZEB2, and Twist in the same panel of cells (Fig. 7, A–C). Depletion of the induced Snail1 levels by the shRNA led to a concomitant and significant decrease in Snail2, ZEB1, and ZEB2 mRNA levels. In the case of ZEB1 and ZEB2, their expression was decreased almost down to the levels of the parental epithelial cells (NMuMG-m). In contrast, Twist levels remained unaltered by the knock-down of endogenous Snail1 (Fig. 7C). These results demonstrate that Snail1 regulates specifically the expression of Snail2, ZEB1, and ZEB2 but not that of Twist. The data suggest that HMGA2 causes EMT by inducing at least two primary transcriptional mediators of this process, Snail1 and Twist. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281169 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18832382 |
We then analyzed the effect of Snail1 depletion on expression of the other four E-cadherin repressors, whose levels become increased by HMGA2 overexpression, Snail2, ZEB1, ZEB2, and Twist in the same panel of cells (Fig. 7, A–C). Depletion of the induced Snail1 levels by the shRNA led to a concomitant and significant decrease in Snail2, ZEB1, and ZEB2 mRNA levels. In the case of ZEB1 and ZEB2, their expression was decreased almost down to the levels of the parental epithelial cells (NMuMG-m). In contrast, Twist levels remained unaltered by the knock-down of endogenous Snail1 (Fig. 7C). These results demonstrate that Snail1 regulates specifically the expression of Snail2, ZEB1, and ZEB2 but not that of Twist. The data suggest that HMGA2 causes EMT by inducing at least two primary transcriptional mediators of this process, Snail1 and Twist. |
|
| Publications: |
2 |
Organism: |
Canidae, Homo Sapiens |
| + |
ZEB1 | down-regulates quantity by repression 
transcriptional regulation
|
GRHL2 |
0.437 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255623 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 23814079 |
we could further demonstrate that expression of GRHL2 is directly suppressed by the transcription factor zinc finger enhancer-binding protein 1 (ZEB1), which in turn is a direct target for repression by GRHL2, suggesting that the EMT transcription factors GRHL2 and ZEB1 form a double negative regulatory feedback loop in breast cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZEB1 | down-regulates quantity by repression
transcriptional regulation
|
EPCAM |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255622 |
|
|
Homo sapiens |
Breast Cancer Cell, Pancreatic Cancer Cell |
| pmid |
sentence |
| 23667256 |
We found a similar ZEB1-dependent repression of EPCAM expression in human pancreatic and breast cancer cell lines, mediated through direct binding of ZEB1 to the EPCAM promoter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SMARCA4 | up-regulates
binding
|
ZEB1 |
0.405 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165017 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20418909 |
Zeb1 represses e-cadherin transcription / we reported that brg1 binds to the ntr of zeb1 acting as its co-repressor in the regulation of the e-cadherin promoter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FBXO45 | down-regulates quantity by destabilization
binding
|
ZEB1 |
0.287 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272179 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25460509 |
One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (UPS). The key step is recognition of EMT-TFs by Fbxo45 through its SPRY domain for Zeb2, or F-box domain for the other three EMT-TFs Snai1, Snai2 and Twist1, respectively. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZEB1 | down-regulates quantity by repression
transcriptional regulation
|
CDH1 |
0.688 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255158 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15311212 |
Known E-cadherin transcriptional repressors, such as SLUG (SNAI2), SIP1 (ZEB2), TWIST1, SNAIL (SNAI1) and ZEB1 (TCF8), but not E12/E47 (TCF3), had a lack of upregulation in cells expressing mutated E-cadherin compared to WT. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GRHL2 | down-regulates quantity by repression
transcriptional regulation
|
ZEB1 |
0.437 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255624 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 23814079 |
we could further demonstrate that expression of GRHL2 is directly suppressed by the transcription factor zinc finger enhancer-binding protein 1 (ZEB1), which in turn is a direct target for repression by GRHL2, suggesting that the EMT transcription factors GRHL2 and ZEB1 form a double negative regulatory feedback loop in breast cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SALL4 | up-regulates quantity by expression 
transcriptional regulation
|
ZEB1 |
0.254 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255123 |
|
|
Homo sapiens |
Breast Cancer Cell Line |
| pmid |
sentence |
| 23954296 |
Our shRNA-mediated SALL4 knockdown system and SALL4 overexpression system revealed that SALL4 suppresses the expression of adhesion gene CDH1, and positively regulates the CDH1 suppressor ZEB1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
LBX1 | up-regulates quantity by expression
transcriptional regulation
|
ZEB1 |
0.329 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266054 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 19651985 |
Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ZEB1 | down-regulates quantity by repression
transcriptional regulation
|
FBP1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267596 |
|
|
Homo sapiens |
Lung Cancer Cell Line |
| pmid |
sentence |
| 30616754 |
Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells|we confirmed DNA methylation in the promoter contributed to the decrease of FBP1 expression in lung cancer cells. We identified Zinc finger E-box-binding homeobox 1 (ZEB1) bond to FBP1 promoter to enhance DNA methylation in lung cancer cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Skp1-Pam E3 | down-regulates quantity by destabilization
polyubiquitination
|
ZEB1 |
0.251 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272186 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25460509 |
One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (UPS). The key step is recognition of EMT-TFs by Fbxo45 through its SPRY domain for Zeb2, or F-box domain for the other three EMT-TFs Snai1, Snai2 and Twist1, respectively. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
miR-429 | down-regulates quantity by destabilization
post transcriptional regulation
|
ZEB1 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281200 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18376396 |
On the basis of the preceding observations, we surmised that a function of miR-205 and the miR-200 family is to prevent expression of ZEB1 and SIP1 in epithelial cells, which may otherwise trigger EMT by downregulating E-cadherin, and further, that downregulation of the microRNAs may be sufficient to initiate EMT. To test this, we examined the effect of the microRNA inhibitors on cell phenotype.We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez.Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as δEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
DAB2IP | down-regulates quantity by repression
transcriptional regulation
|
ZEB1 |
0.269 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254772 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27858941 |
Through inhibition of PI3K–AKT signaling, DAB2IP also represses ZEB1, another CSC determinant. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
ZEB1
- 
- 