Ferroptosis Regulator Information
General Information of the Ferroptosis Regulator (ID: REG10306)
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
NEDD4L
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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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Glioblastoma | ICD-11: 2A00 | |||
Responsed Drug | Peoniflorin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
U-251MG cells | Astrocytoma | Homo sapiens | CVCL_0021 | |
U87 MG-Red-Fluc cells | Glioblastoma | Homo sapiens | CVCL_5J12 | ||
In Vivo Model |
U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining.
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Response regulation | Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. | ||||
Experiment 2 Reporting the Ferroptosis Target of This Regulator | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Lung cancer | ICD-11: 2C25 | |||
Responsed Drug | Lactate | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | |
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
NCI-H446 cells | Lung small cell carcinoma | Homo sapiens | CVCL_1562 | ||
NCI-H1688 cells | Lung small cell carcinoma | Homo sapiens | CVCL_1487 | ||
Response regulation | Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in Non-Small Cell Lung Cancer (NSCLC). Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38 (MAPK14)-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. | ||||
Experiment 3 Reporting the Ferroptosis Target of This Regulator | [3] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian dysfunction | ICD-11: 5A80 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
KGN cells | Ovarian granulosa cell tumor | Homo sapiens | CVCL_0375 | |
In Vivo Model |
Adult female C57BL/6J mice were purchased from Cyagen Bioscience (Santa Clara, CA, USA). Prior to the experiment, the animals were allowed to adapt to the environment for 1 week. For this study, all procedures were approved by the Ethics Committee of Shanghai Seventh Peoples Hospital (item number: 2021-AR-059). Adult female C57BL/6J mice were housed withaccess to food and waterad libitum. The PCOS mouse model was established as described previously. In brief, female C57BL/6J mice (4 weeks old) were subcutaneously injected with DHEA (6 mg/0.1kg body weight) daily for 20 days.
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Response regulation | NEDD4L facilitates GC ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of polycystic ovary syndrome. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [1] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Glioblastoma | ICD-11: 2A00 | |||
Responsed Drug | Peoniflorin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
U-251MG cells | Astrocytoma | Homo sapiens | CVCL_0021 | |
U87 MG-Red-Fluc cells | Glioblastoma | Homo sapiens | CVCL_5J12 | ||
In Vivo Model |
U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining.
Click to Show/Hide
|
||||
Response regulation | Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. | ||||
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [4] | |||
Target for Ferroptosis | Suppressor | |||
Responsed Disease | Breast cancer | ICD-11: 2C60 | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ubiquitin mediated proteolysis | hsa04120 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
MCF-7 cells | Breast carcinoma | Homo sapiens | CVCL_0031 |
ZR-75-1 cells | Invasive breast carcinoma | Homo sapiens | CVCL_0588 | |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Response regulation | SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, the study elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer. | |||
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis Target of This Regulator | [5] | |||
Responsed Disease | Pancreatic cancer | ICD-11: 2C10 | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | |
Response regulation | The study screened 571 UPS-related E1, E2, and E3 genes in a human pancreatic cancer cell line (PANC1) and identified the upregulation of NEDD4-like E3 ubiquitin protein ligase (NEDD4L) as a novel ferroptosis suppressor. NEDD4L-mediated LTF protein degradation inhibits intracellular iron accumulation and subsequent oxidative damage-mediated ferroptotic cell death. | |||
Glioblastoma [ICD-11: 2A00]
In total 2 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) | Protein coding | |||
Responsed Drug | Peoniflorin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
U-251MG cells | Astrocytoma | Homo sapiens | CVCL_0021 | |
U87 MG-Red-Fluc cells | Glioblastoma | Homo sapiens | CVCL_5J12 | ||
In Vivo Model |
U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining.
Click to Show/Hide
|
||||
Response regulation | Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response | [1] | ||||
Target Regulator | E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) | Protein coding | |||
Responsed Drug | Peoniflorin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
U-251MG cells | Astrocytoma | Homo sapiens | CVCL_0021 | |
U87 MG-Red-Fluc cells | Glioblastoma | Homo sapiens | CVCL_5J12 | ||
In Vivo Model |
U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining.
Click to Show/Hide
|
||||
Response regulation | Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. | ||||
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [2] | |||
Target Regulator | E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) | Protein coding | ||
Responsed Drug | Lactate | Investigative | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ubiquitin mediated proteolysis | hsa04120 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 |
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | |
NCI-H446 cells | Lung small cell carcinoma | Homo sapiens | CVCL_1562 | |
NCI-H1688 cells | Lung small cell carcinoma | Homo sapiens | CVCL_1487 | |
Response regulation | Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in Non-Small Cell Lung Cancer (NSCLC). Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38 (MAPK14)-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. | |||
Breast cancer [ICD-11: 2C60]
In total 1 item(s) under this disease | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [4] | |||
Target Regulator | E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) | Protein coding | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ubiquitin mediated proteolysis | hsa04120 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
MCF-7 cells | Breast carcinoma | Homo sapiens | CVCL_0031 |
ZR-75-1 cells | Invasive breast carcinoma | Homo sapiens | CVCL_0588 | |
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | |
Response regulation | SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, the study elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer. | |||
Ovarian dysfunction [ICD-11: 5A80]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [3] | ||||
Target Regulator | E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) | Protein coding | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
KGN cells | Ovarian granulosa cell tumor | Homo sapiens | CVCL_0375 | |
In Vivo Model |
Adult female C57BL/6J mice were purchased from Cyagen Bioscience (Santa Clara, CA, USA). Prior to the experiment, the animals were allowed to adapt to the environment for 1 week. For this study, all procedures were approved by the Ethics Committee of Shanghai Seventh Peoples Hospital (item number: 2021-AR-059). Adult female C57BL/6J mice were housed withaccess to food and waterad libitum. The PCOS mouse model was established as described previously. In brief, female C57BL/6J mice (4 weeks old) were subcutaneously injected with DHEA (6 mg/0.1kg body weight) daily for 20 days.
Click to Show/Hide
|
||||
Response regulation | NEDD4L facilitates GC ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of polycystic ovary syndrome. | ||||
Pancreatic cancer [ICD-11: 2C10]
In total 1 item(s) under this disease | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response | [5] | |||
Target Regulator | E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) | Protein coding | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | |
Response regulation | The study screened 571 UPS-related E1, E2, and E3 genes in a human pancreatic cancer cell line (PANC1) and identified the upregulation of NEDD4-like E3 ubiquitin protein ligase (NEDD4L) as a novel ferroptosis suppressor. NEDD4L-mediated LTF protein degradation inhibits intracellular iron accumulation and subsequent oxidative damage-mediated ferroptotic cell death. | |||
Peoniflorin
[Investigative]
In total 2 item(s) under this drug | |||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | Phospholipid hydroperoxide glutathione peroxidase (GPX4) | Suppressor | |||
Responsed Disease | Glioblastoma | ICD-11: 2A00 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
U-251MG cells | Astrocytoma | Homo sapiens | CVCL_0021 | |
U87 MG-Red-Fluc cells | Glioblastoma | Homo sapiens | CVCL_5J12 | ||
In Vivo Model |
U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining.
Click to Show/Hide
|
||||
Response regulation | Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. | ||||
Experiment 2 Reporting the Ferroptosis-centered Drug Response | [1] | ||||
Drug for Ferroptosis | Inducer | ||||
Response Target | Nuclear factor erythroid 2-related factor 2 (NFE2L2) | Suppressor; Marker | |||
Responsed Disease | Glioblastoma | ICD-11: 2A00 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
U-251MG cells | Astrocytoma | Homo sapiens | CVCL_0021 | |
U87 MG-Red-Fluc cells | Glioblastoma | Homo sapiens | CVCL_5J12 | ||
In Vivo Model |
U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining.
Click to Show/Hide
|
||||
Response regulation | Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. | ||||
Lactate
[Investigative]
In total 1 item(s) under this drug | ||||
Experiment 1 Reporting the Ferroptosis-centered Drug Response | [2] | |||
Drug for Ferroptosis | Suppressor | |||
Response Target | Phospholipid hydroperoxide glutathione peroxidase (GPX4) | Suppressor | ||
Responsed Disease | Lung cancer | ICD-11: 2C25 | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ubiquitin mediated proteolysis | hsa04120 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model |
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 |
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | |
NCI-H446 cells | Lung small cell carcinoma | Homo sapiens | CVCL_1562 | |
NCI-H1688 cells | Lung small cell carcinoma | Homo sapiens | CVCL_1487 | |
Response regulation | Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in Non-Small Cell Lung Cancer (NSCLC). Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38 (MAPK14)-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. | |||
References