Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10502)
Regulator Name Transcription factor AP-2-alpha (TFAP2A)
Synonyms
AP2TF; TFAP2; AP-2 transcription factor; Activating enhancer-binding protein 2-alpha; Activator protein 2
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Gene Name TFAP2A
Gene ID 7020
Regulator Type Protein coding
Uniprot ID P05549
Sequence
MLWKLTDNIKYEDCEDRHDGTSNGTARLPQLGTVGQSPYTSAPPLSHTPNADFQPPYFPP
PYQPIYPQSQDPYSHVNDPYSLNPLHAQPQPQHPGWPGQRQSQESGLLHTHRGLPHQLSG
LDPRRDYRRHEDLLHGPHALSSGLGDLSIHSLPHAIEEVPHVEDPGINIPDQTVIKKGPV
SLSKSNSNAVSAIPINKDNLFGGVVNPNEVFCSVPGRLSLLSSTSKYKVTVAEVQRRLSP
PECLNASLLGGVLRRAKSKNGGRSLREKLDKIGLNLPAGRRKAANVTLLTSLVEGEAVHL
ARDFGYVCETEFPAKAVAEFLNRQHSDPNEQVTRKNMLLATKQICKEFTDLLAQDRSPLG
NSRPNPILEPGIQSCLTHFNLISHGFGSPAVCAAVTALQNYLTEALKAMDKMYLSNNPNS
HTDNNAKSSDKEEKHRK

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Family AP-2 family
Function
Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region.

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HGNC ID
HGNC:11742
KEGG ID hsa:7020
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TFAP2A can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Browse Disease
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Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Responsed Drug Solasonine Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
CFPAC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_1119
In Vivo Model
For xenograft assays, we subcutaneously injected 1 x 106 PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment.

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Response regulation Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis.
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Gallbladder cancer ICD-11: 2C13
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
NAD(P)H dehydrogenase [quinone] 1 (NQO1) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Gallbladder cancer ICD-11: 2C13
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Heme oxygenase 1 (HMOX1) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Driver/Suppressor
Responsed Disease Gallbladder cancer ICD-11: 2C13
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Ferritin heavy chain (FTH1) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Gallbladder cancer ICD-11: 2C13
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcription factor AP-2-alpha (TFAP2A) Protein coding
 Regulator Info 
Responsed Drug Solasonine Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
CFPAC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_1119
In Vivo Model
For xenograft assays, we subcutaneously injected 1 x 106 PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment.

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Response regulation Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis.
Gallbladder cancer [ICD-11: 2C13]
 Disease Info 
In total 4 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Transcription factor AP-2-alpha (TFAP2A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Transcription factor AP-2-alpha (TFAP2A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Experiment 3 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Transcription factor AP-2-alpha (TFAP2A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Experiment 4 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Transcription factor AP-2-alpha (TFAP2A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 H69 cells Normal Homo sapiens CVCL_8121
GBC-SD cells Gallbladder carcinoma Homo sapiens CVCL_6903
Response regulation In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).
Solasonine [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Cystine/glutamate transporter (SLC7A11) Driver; Suppressor
 Target Info 
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
CFPAC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_1119
In Vivo Model
For xenograft assays, we subcutaneously injected 1 x 106 PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment.

    Click to Show/Hide
Response regulation Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis.
References
Ref 1 Solasonine Inhibits Pancreatic Cancer Progression With Involvement of Ferroptosis Induction. Front Oncol. 2022 Apr 12;12:834729. doi: 10.3389/fonc.2022.834729. eCollection 2022.
Ref 2 TFAP2A is a novel regulator that modulates ferroptosis in gallbladder carcinoma cells via the Nrf2 signalling axis. Eur Rev Med Pharmacol Sci. 2020 May;24(9):4745-4755. doi: 10.26355/eurrev_202005_21163.