Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10246)
Regulator Name Autophagy-related protein 16-1
Synonyms
APG16-like 1
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Gene ID 55054
Regulator Type Protein coding
Uniprot ID Q676U5
Sequence
MSSGLRAADFPRWKRHISEQLRRRDRLQRQAFEEIILQYNKLLEKSDLHSVLAQKLQAEK
HDVPNRHEISPGHDGTWNDNQLQEMAQLRIKHQEELTELHKKRGELAQLVIDLNNQMQRK
DREMQMNEAKIAECLQTISDLETECLDLRTKLCDLERANQTLKDEYDALQITFTALEGKL
RKTTEENQELVTRWMAEKAQEANRLNAENEKDSRRRQARLQKELAEAAKEPLPVEQDDDI
EVIVDETSDHTEETSPVRAISRAATKRLSQPAGGLLDSITNIFGRRSVSSFPVPQDNVDT
HPGSGKEVRVPATALCVFDAHDGEVNAVQFSPGSRLLATGGMDRRVKLWEVFGEKCEFKG
SLSGSNAGITSIEFDSAGSYLLAASNDFASRIWTVDDYRLRHTLTGHSGKVLSAKFLLDN
ARIVSGSHDRTLKLWDLRSKVCIKTVFAGSSCNDIVCTEQCVMSGHFDKKIRFWDIRSES
IVREMELLGKITALDLNPERTELLSCSRDDLLKVIDLRTNAIKQTFSAPGFKCGSDWTRV
VFSPDGSYVAAGSAEGSLYIWSVLTGKVEKVLSKQHSSSINAVAWSPSGSHVVSVDKGCK
AVLWAQY

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Family WD repeat ATG16 family
Function
Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP). Acts as a molecular hub, coordinating autophagy pathways via distinct domains that support either canonical or non- canonical signaling. During canonical autophagy, interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to ATG8 proteins, to produce a membrane-bound activated form of ATG8. Thereby, controls the elongation of the nascent autophagosomal membrane. Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, probably by catalyzing conjugation of phosphatidylserine (PS) to ATG8. Non-canonical autophagy plays a key role in epithelial cells to limit lethal infection by influenza A (IAV) virus. Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production. Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response. Instead, promotes with NOD2 an autophagy-dependent antibacterial pathway. Plays a role in regulating morphology and function of Paneth cell.

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HGNC ID
HGNC:21498
KEGG ID hsa:55054
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
Autophagy-related protein 16-1 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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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 [1]
Target for Ferroptosis Driver
Responsed Disease Liver fibrosis ICD-11: DB93
 Disease Info 
Responsed Drug Sorafenib Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 hHSCs (Human hepatic stellate cells)
In Vivo Model
Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation.

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Response regulation Sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. ATG16L1 plasmid eliminated the inhibitory action of ZFP36 plasmid on ferroptosis, and FBXW7 plasmid enhanced the effect of ATG16L1 plasmid on autophagy. ZFP36 plasmid markedly upregulated, whereas FBXW7 plasmid apparently downregulaed, ferritin and NCOA4 expression in sorafenib-treated HSC-LX2 cells. The study identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis.
Liver fibrosis [ICD-11: DB93]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Autophagy-related protein 16-1 Protein coding
 Regulator Info 
Responsed Drug Sorafenib Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 hHSCs (Human hepatic stellate cells)
In Vivo Model
Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation.

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Response regulation Sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. ATG16L1 plasmid eliminated the inhibitory action of ZFP36 plasmid on ferroptosis, and FBXW7 plasmid enhanced the effect of ATG16L1 plasmid on autophagy. ZFP36 plasmid markedly upregulated, whereas FBXW7 plasmid apparently downregulaed, ferritin and NCOA4 expression in sorafenib-treated HSC-LX2 cells. The study identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis.
Sorafenib [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 Nuclear receptor coactivator 4 (NCOA4) Driver
 Target Info 
Responsed Disease Liver fibrosis ICD-11: DB93
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 hHSCs (Human hepatic stellate cells)
In Vivo Model
Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation.

    Click to Show/Hide
Response regulation Sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. ATG16L1 plasmid eliminated the inhibitory action of ZFP36 plasmid on ferroptosis, and FBXW7 plasmid enhanced the effect of ATG16L1 plasmid on autophagy. ZFP36 plasmid markedly upregulated, whereas FBXW7 plasmid apparently downregulaed, ferritin and NCOA4 expression in sorafenib-treated HSC-LX2 cells. The study identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis.
References
Ref 1 RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy. 2020 Aug;16(8):1482-1505. doi: 10.1080/15548627.2019.1687985. Epub 2019 Nov 11.