Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10338)
Regulator Name Autophagy protein 5 (ATG5)
Synonyms
APG5L, ASP; APG5-like; Apoptosis-specific protein
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Gene Name ATG5
Gene ID 9474
Regulator Type Protein coding
Uniprot ID Q9H1Y0
Sequence
MTDDKDVLRDVWFGRIPTCFTLYQDEITEREAEPYYLLLPRVSYLTLVTDKVKKHFQKVM
RQEDISEIWFEYEGTPLKWHYPIGLLFDLLASSSALPWNITVHFKSFPEKDLLHCPSKDA
IEAHFMSCMKEADALKHKSQVINEMQKKDHKQLWMGLQNDRFDQFWAINRKLMEYPAEEN
GFRYIPFRIYQTTTERPFIQKLFRPVAADGQLHTLGDLLKEVCPSAIDPEDGEKKNQVMI
HGIEPMLETPLQWLSEHLSYPDNFLHISIIPQPTD

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Family ATG5 family
Function
Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3- like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.

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HGNC ID
HGNC:589
KEGG ID hsa:9474
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
ATG5 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
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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 [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Drug Amentoflavone Investigative
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
 U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
In Vivo Model
1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively.

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Response regulation Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma.
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Oesophageal cancer ICD-11: 2B70
 Disease Info 
Responsed Drug Allicin Investigative
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE-510 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1354
HET-1A cells Normal Homo sapiens CVCL_3702
In Vivo Model
All mice were housed in a specific pathogen-free environment under a standard 12 h light-dark cycle at 25 and had ad libitum access to food and water. Approximately 4 x 106 KYSE510 cells in 100 uL of normal saline were subcutaneously injected into the right flank of mice (n = 20 in total). All mice were allocated to a control or 10 mg/kg allicin group (n = 10 per group), as previously described (Suddek 2014). The mice were orally administered allicin or normal saline once daily for 28 days.

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Response regulation In summary, allicin may induce cell death in esophageal squamous cell carcinoma (ESCC) cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Furthermore, ATG5 and ATG7 expression increased in tumors after allicin treatment. In contrast, NCOA4 expression increased, but the protein level of FTH1 and TfR1 decreased in tumors after allicin treatment.
Nuclear receptor coactivator 4 (NCOA4) [Driver]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [3]
Target for Ferroptosis Driver
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 mEFs (Mouse embryonic fibroblasts)
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Panc 02.03 cells Pancreatic adenocarcinoma Homo sapiens CVCL_1633
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Response regulation Autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and pancreatic cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis.
Glioblastoma [ICD-11: 2A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Autophagy protein 5 (ATG5) Protein coding
 Regulator Info 
Responsed Drug Amentoflavone Investigative
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
 U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
In Vivo Model
1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively.

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Response regulation Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma.
Oesophageal cancer [ICD-11: 2B70]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Autophagy protein 5 (ATG5) Protein coding
 Regulator Info 
Responsed Drug Allicin Investigative
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE-510 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1354
HET-1A cells Normal Homo sapiens CVCL_3702
In Vivo Model
All mice were housed in a specific pathogen-free environment under a standard 12 h light-dark cycle at 25 and had ad libitum access to food and water. Approximately 4 x 106 KYSE510 cells in 100 uL of normal saline were subcutaneously injected into the right flank of mice (n = 20 in total). All mice were allocated to a control or 10 mg/kg allicin group (n = 10 per group), as previously described (Suddek 2014). The mice were orally administered allicin or normal saline once daily for 28 days.

    Click to Show/Hide
Response regulation In summary, allicin may induce cell death in esophageal squamous cell carcinoma (ESCC) cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Furthermore, ATG5 and ATG7 expression increased in tumors after allicin treatment. In contrast, NCOA4 expression increased, but the protein level of FTH1 and TfR1 decreased in tumors after allicin treatment.
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Autophagy protein 5 (ATG5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 mEFs (Mouse embryonic fibroblasts)
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Panc 02.03 cells Pancreatic adenocarcinoma Homo sapiens CVCL_1633
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Response regulation Autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and pancreatic cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis.
Amentoflavone [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 Ferritin heavy chain (FTH1) Suppressor; Marker
 Target Info 
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
 U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
In Vivo Model
1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively.

    Click to Show/Hide
Response regulation Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma.
Allicin [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 Oesophageal cancer ICD-11: 2B70
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE-510 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1354
HET-1A cells Normal Homo sapiens CVCL_3702
In Vivo Model
All mice were housed in a specific pathogen-free environment under a standard 12 h light-dark cycle at 25 and had ad libitum access to food and water. Approximately 4 x 106 KYSE510 cells in 100 uL of normal saline were subcutaneously injected into the right flank of mice (n = 20 in total). All mice were allocated to a control or 10 mg/kg allicin group (n = 10 per group), as previously described (Suddek 2014). The mice were orally administered allicin or normal saline once daily for 28 days.

    Click to Show/Hide
Response regulation In summary, allicin may induce cell death in esophageal squamous cell carcinoma (ESCC) cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Furthermore, ATG5 and ATG7 expression increased in tumors after allicin treatment. In contrast, NCOA4 expression increased, but the protein level of FTH1 and TfR1 decreased in tumors after allicin treatment.
References
Ref 1 Amentoflavone suppresses cell proliferation and induces cell death through triggering autophagy-dependent ferroptosis in human glioma. Life Sci. 2020 Apr 15;247:117425. doi: 10.1016/j.lfs.2020.117425. Epub 2020 Feb 11.
Ref 2 Allicin promotes autophagy and ferroptosis in esophageal squamous cell carcinoma by activating AMPK/mTOR signaling. Heliyon. 2022 Oct 12;8(10):e11005. doi: 10.1016/j.heliyon.2022.e11005. eCollection 2022 Oct.
Ref 3 Autophagy promotes ferroptosis by degradation of ferritin. Autophagy. 2016 Aug 2;12(8):1425-8. doi: 10.1080/15548627.2016.1187366. Epub 2016 May 31.