Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10392)
Regulator Name E3 ubiquitin-protein ligase Mdm2 (MDM2)
Synonyms
Double minute 2 protein (Hdm2); Oncoprotein Mdm2; RING-type E3 ubiquitin transferase Mdm2; p53-binding protein Mdm2
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Gene Name MDM2
Gene ID 4193
Regulator Type Protein coding
Uniprot ID Q00987
Sequence
MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQY
IMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGT
SVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQ
RKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDS
VSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLA
DYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVP
DCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQ
DKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQ
PIQMIVLTYFP

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Family MDM2/MDM4 family
Function
E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also a component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation.

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HGNC ID
HGNC:6973
KEGG ID hsa:4193
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
MDM2 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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Ferroptosis suppressor protein 1 (AIFM2) [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 Colon cancer ICD-11: 2B90
 Disease Info 
Responsed Drug Nutlin-3 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Response regulation Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma.
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Colon cancer ICD-11: 2B90
 Disease Info 
Responsed Drug Ginkgo biflavones Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
RKO cells Colon carcinoma Homo sapiens CVCL_0504
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
In Vivo Model
HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately).

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Response regulation Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
Colon cancer [ICD-11: 2B90]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator E3 ubiquitin-protein ligase Mdm2 (MDM2) Protein coding
 Regulator Info 
Responsed Drug Nutlin-3 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Response regulation Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator E3 ubiquitin-protein ligase Mdm2 (MDM2) Protein coding
 Regulator Info 
Responsed Drug Ginkgo biflavones Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
RKO cells Colon carcinoma Homo sapiens CVCL_0504
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
In Vivo Model
HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately).

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Response regulation Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
Nutlin-3 [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Ferroptosis suppressor protein 1 (AIFM2) Suppressor
 Target Info 
Responsed Disease Colon cancer ICD-11: 2B90
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Response regulation Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma.
Ginkgo biflavones [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [2]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Colon cancer ICD-11: 2B90
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HT29 cells Colon cancer Mus musculus CVCL_A8EZ
RKO cells Colon carcinoma Homo sapiens CVCL_0504
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
In Vivo Model
HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately).

    Click to Show/Hide
Response regulation Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
References
Ref 1 MDM2 and MDMX promote ferroptosis by PPAR-mediated lipid remodeling. Genes Dev. 2020 Apr 1;34(7-8):526-543. doi: 10.1101/gad.334219.119. Epub 2020 Feb 20.
Ref 2 Ginkgo Biflavones Cause p53 Wild-Type Dependent Cell Death in a Transcription-Independent Manner of p53. J Nat Prod. 2023 Feb 24;86(2):346-356. doi: 10.1021/acs.jnatprod.2c00959. Epub 2023 Jan 26.