Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10276)
Regulator Name Tumor suppressor ARF (CDKN2A)
Synonyms
Alternative reading frame
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Gene Name CDKN2A
Gene ID 1029
Regulator Type Protein coding
Uniprot ID Q8N726
Sequence
MVRRFLVTLRIRRACGPPRVRVFVVHIPRLTGEWAAPGAPAAVALVLMLLRSQRLGQQPL
PRRPGHDDGQRPSGGAAAAPRRGAQLRRPRHSHPTRARRCPGGLPGHAGGAAPGRGAAGR
ARCLGPSARGPG

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Function
Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing. Plays a role in inhibiting ribosome biogenesis, perhaps by binding to the nucleolar localization sequence of transcription termination factor TTF1, and thereby preventing nucleolar localization of TTF1. Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination. Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1. Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and apoptosis during mammary gland development.

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HGNC ID
HGNC:1787
KEGG ID hsa:1029
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CDKN2A 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).
Browse Target
Browse Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293 cells Normal Homo sapiens CVCL_0045
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
In Vivo Model
Pooled stable cell line was derived from H1299 tet-on ARF cells by transfecting either empty vector or vector overexpressing NRF2. Cells were selected by G418 (1 mg /ml) for 2 weeks and then re-transfected the same vectors again. After additional treatment with or without doxycycline (1.0 mg/ml) for 60 h, 1.0 x 106 of cells were then mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) and injected subcutaneously into nude mice (NU/NU, Charles River). The mice were fed with the food containing doxycycline hyclate (Harlan, 625 mg/kg) or control food.

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Response regulation ARF (CDKN2A) expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses in lung large cell carcinoma cell lines.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293 cells Normal Homo sapiens CVCL_0045
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
In Vivo Model
Pooled stable cell line was derived from H1299 tet-on ARF cells by transfecting either empty vector or vector overexpressing NRF2. Cells were selected by G418 (1 mg /ml) for 2 weeks and then re-transfected the same vectors again. After additional treatment with or without doxycycline (1.0 mg/ml) for 60 h, 1.0 x 106 of cells were then mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) and injected subcutaneously into nude mice (NU/NU, Charles River). The mice were fed with the food containing doxycycline hyclate (Harlan, 625 mg/kg) or control food.

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Response regulation ARF (CDKN2A) expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses in Lung adenocarcinomaLung adenocarcinoma.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Tumor suppressor ARF (CDKN2A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293 cells Normal Homo sapiens CVCL_0045
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
In Vivo Model
Pooled stable cell line was derived from H1299 tet-on ARF cells by transfecting either empty vector or vector overexpressing NRF2. Cells were selected by G418 (1 mg /ml) for 2 weeks and then re-transfected the same vectors again. After additional treatment with or without doxycycline (1.0 mg/ml) for 60 h, 1.0 x 106 of cells were then mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) and injected subcutaneously into nude mice (NU/NU, Charles River). The mice were fed with the food containing doxycycline hyclate (Harlan, 625 mg/kg) or control food.

    Click to Show/Hide
Response regulation ARF (CDKN2A) expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses in lung large cell carcinoma cell lines.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Tumor suppressor ARF (CDKN2A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293 cells Normal Homo sapiens CVCL_0045
SAOS-2 cells Osteosarcoma Homo sapiens CVCL_0548
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
In Vivo Model
Pooled stable cell line was derived from H1299 tet-on ARF cells by transfecting either empty vector or vector overexpressing NRF2. Cells were selected by G418 (1 mg /ml) for 2 weeks and then re-transfected the same vectors again. After additional treatment with or without doxycycline (1.0 mg/ml) for 60 h, 1.0 x 106 of cells were then mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) and injected subcutaneously into nude mice (NU/NU, Charles River). The mice were fed with the food containing doxycycline hyclate (Harlan, 625 mg/kg) or control food.

    Click to Show/Hide
Response regulation ARF (CDKN2A) expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses in Lung adenocarcinomaLung adenocarcinoma.
References
Ref 1 NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression. Mol Cell. 2017 Oct 5;68(1):224-232.e4. doi: 10.1016/j.molcel.2017.09.009.