Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10403)
Regulator Name Transcription factor Sp1 (SP1)
Synonyms
TSFP1
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Gene Name SP1
Gene ID 6667
Regulator Type Protein coding
Uniprot ID P08047
Sequence
MSDQDHSMDEMTAVVKIEKGVGGNNGGNGNGGGAFSQARSSSTGSSSSTGGGGQESQPSP
LALLAATCSRIESPNENSNNSQGPSQSGGTGELDLTATQLSQGANGWQIISSSSGATPTS
KEQSGSSTNGSNGSESSKNRTVSGGQYVVAAAPNLQNQQVLTGLPGVMPNIQYQVIPQFQ
TVDGQQLQFAATGAQVQQDGSGQIQIIPGANQQIITNRGSGGNIIAAMPNLLQQAVPLQG
LANNVLSGQTQYVTNVPVALNGNITLLPVNSVSAATLTPSSQAVTISSSGSQESGSQPVT
SGTTISSASLVSSQASSSSFFTNANSYSTTTTTSNMGIMNFTTSGSSGTNSQGQTPQRVS
GLQGSDALNIQQNQTSGGSLQAGQQKEGEQNQQTQQQQILIQPQLVQGGQALQALQAAPL
SGQTFTTQAISQETLQNLQLQAVPNSGPIIIRTPTVGPNGQVSWQTLQLQNLQVQNPQAQ
TITLAPMQGVSLGQTSSSNTTLTPIASAASIPAGTVTVNAAQLSSMPGLQTINLSALGTS
GIQVHPIQGLPLAIANAPGDHGAQLGLHGAGGDGIHDDTAGGEEGENSPDAQPQAGRRTR
REACTCPYCKDSEGRGSGDPGKKKQHICHIQGCGKVYGKTSHLRAHLRWHTGERPFMCTW
SYCGKRFTRSDELQRHKRTHTGEKKFACPECPKRFMRSDHLSKHIKTHQNKKGGPGVALS
VGTLPLDSGAGSEGSGTATPSALITTNMVAMEAICPEGIARLANSGINVMQVADLQSINI
SGNGF

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Family Sp1 C2H2-type zinc-finger protein family
Function
Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 ( , , , , , , , , , , , , , , , , ). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). { |UniProtKB:O89090, |UniProtKB:Q01714, | , | , | , | , | , | , | , | , | , | , | , | , | , | , | , | , | }.

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HGNC ID
HGNC:11205
KEGG ID hsa:6667
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SP1 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
Browse Drug
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) [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 Cerebral ischemia ICD-11: 8B10
 Disease Info 
Responsed Drug Sevoflurane Approved
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Adult male SD rats (250-300 g) were purchased from Charies River (Beijing, China). The animals were placed in laboratory cages, kept on a 12-h light-dark cycle, and had free access to food and water throughout the study. The rats were randomly assigned to the sham (only the left neck was exposed without ligation) group, MACO group, and sevo + MACO (2.5% sevoflurane before refusion) group. The MCAO model was made by a modified nylon suture method. After 1 h of ischemia, the suture was gently pulled to the beginning of the external carotid artery and re-perfused for 24 h. For sevoflurane postconditioning, rats were stabilized in a gas-tight anesthesia chamber with sevoflurane inhalation for 1 h at the onset of blood refusion. Sevoflurane (AbbVie, Japan) was delivered at a concentration of 2.5% through a vaporizer (Vapor 2000, Germany). In the sham or MCAO group, rats were only exposed to the mixed gas (95% O2 and 5% CO2).

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Response regulation Sevoflurane treatment inhibits ferroptosis and increases apoptosis events by inhibiting the SP1/ASCL4 axis, thereby reducing cerebral ischemia-reperfusion injury damage.
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Chronic kidney disease ICD-11: GB61
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MPC-5 cells Normal Mus musculus CVCL_AS87
In Vivo Model
Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established.

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Response regulation Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice.
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Endotheliitis ICD-11: 1F00
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
In Vitro Model
 hEPCs (Endothelial progenitor cells)
HUVECs (Human umbilical vein endothelial cells)
Response regulation EPCs-Exos inhibited Erastin-induced HUVEC ferroptosis and endothelial injury. EPCs-Exos promoted the activation of the AMPK pathway by upregulating the expression of miR-30e-5p in HUVECs and inhibiting the expression of SP1 in HUVECs, thus inhibiting Erastin-induced cell ferroptosis.
Cerebral ischemia [ICD-11: 8B10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcription factor Sp1 (SP1) Protein coding
 Regulator Info 
Responsed Drug Sevoflurane Approved
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Adult male SD rats (250-300 g) were purchased from Charies River (Beijing, China). The animals were placed in laboratory cages, kept on a 12-h light-dark cycle, and had free access to food and water throughout the study. The rats were randomly assigned to the sham (only the left neck was exposed without ligation) group, MACO group, and sevo + MACO (2.5% sevoflurane before refusion) group. The MCAO model was made by a modified nylon suture method. After 1 h of ischemia, the suture was gently pulled to the beginning of the external carotid artery and re-perfused for 24 h. For sevoflurane postconditioning, rats were stabilized in a gas-tight anesthesia chamber with sevoflurane inhalation for 1 h at the onset of blood refusion. Sevoflurane (AbbVie, Japan) was delivered at a concentration of 2.5% through a vaporizer (Vapor 2000, Germany). In the sham or MCAO group, rats were only exposed to the mixed gas (95% O2 and 5% CO2).

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Response regulation Sevoflurane treatment inhibits ferroptosis and increases apoptosis events by inhibiting the SP1/ASCL4 axis, thereby reducing cerebral ischemia-reperfusion injury damage.
Chronic kidney disease [ICD-11: GB61]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Transcription factor Sp1 (SP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MPC-5 cells Normal Mus musculus CVCL_AS87
In Vivo Model
Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established.

    Click to Show/Hide
Response regulation Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice.
Endotheliitis [ICD-11: 1F00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Transcription factor Sp1 (SP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
In Vitro Model
 hEPCs (Endothelial progenitor cells)
HUVECs (Human umbilical vein endothelial cells)
Response regulation EPCs-Exos inhibited Erastin-induced HUVEC ferroptosis and endothelial injury. EPCs-Exos promoted the activation of the AMPK pathway by upregulating the expression of miR-30e-5p in HUVECs and inhibiting the expression of SP1 in HUVECs, thus inhibiting Erastin-induced cell ferroptosis.
Sevoflurane [Approved]
 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 Long-chain-fatty-acid--CoA ligase 4 (ACSL4) Driver
 Target Info 
Responsed Disease Cerebral ischemia ICD-11: 8B10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Adult male SD rats (250-300 g) were purchased from Charies River (Beijing, China). The animals were placed in laboratory cages, kept on a 12-h light-dark cycle, and had free access to food and water throughout the study. The rats were randomly assigned to the sham (only the left neck was exposed without ligation) group, MACO group, and sevo + MACO (2.5% sevoflurane before refusion) group. The MCAO model was made by a modified nylon suture method. After 1 h of ischemia, the suture was gently pulled to the beginning of the external carotid artery and re-perfused for 24 h. For sevoflurane postconditioning, rats were stabilized in a gas-tight anesthesia chamber with sevoflurane inhalation for 1 h at the onset of blood refusion. Sevoflurane (AbbVie, Japan) was delivered at a concentration of 2.5% through a vaporizer (Vapor 2000, Germany). In the sham or MCAO group, rats were only exposed to the mixed gas (95% O2 and 5% CO2).

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Response regulation Sevoflurane treatment inhibits ferroptosis and increases apoptosis events by inhibiting the SP1/ASCL4 axis, thereby reducing cerebral ischemia-reperfusion injury damage.
References
Ref 1 Sevoflurane Postconditioning Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting SP1/ACSL4-Mediated Ferroptosis. Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231160477. doi: 10.1177/09603271231160477.
Ref 2 Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis. Life Sci. 2021 Aug 1;278:119529. doi: 10.1016/j.lfs.2021.119529. Epub 2021 Apr 21.
Ref 3 Endothelial progenitor cells-derived exosomes transfer microRNA-30e-5p to regulate Erastin-induced ferroptosis in human umbilical vein endothelial cells via the specificity protein 1/adenosine monophosphate-activated protein kinase axis. Bioengineered. 2022 Feb;13(2):3566-3580. doi: 10.1080/21655979.2022.2025519.