Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10400)
Regulator Name Polypyrimidine tract-binding protein 1 (PTBP1)
Synonyms
PTB; 57 kDa RNA-binding protein PPTB-1; Heterogeneous nuclear ribonucleoprotein I
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Gene Name PTBP1
Gene ID 5725
Regulator Type Protein coding
Uniprot ID P26599
Sequence
MDGIVPDIAVGTKRGSDELFSTCVTNGPFIMSSNSASAANGNDSKKFKGDSRSAGVPSRV
IHIRKLPIDVTEGEVISLGLPFGKVTNLLMLKGKNQAFIEMNTEEAANTMVNYYTSVTPV
LRGQPIYIQFSNHKELKTDSSPNQARAQAALQAVNSVQSGNLALAASAAAVDAGMAMAGQ
SPVLRIIVENLFYPVTLDVLHQIFSKFGTVLKIITFTKNNQFQALLQYADPVSAQHAKLS
LDGQNIYNACCTLRIDFSKLTSLNVKYNNDKSRDYTRPDLPSGDSQPSLDQTMAAAFGAP
GIISASPYAGAGFPPTFAIPQAAGLSVPNVHGALAPLAIPSAAAAAAAAGRIAIPGLAGA
GNSVLLVSNLNPERVTPQSLFILFGVYGDVQRVKILFNKKENALVQMADGNQAQLAMSHL
NGHKLHGKPIRITLSKHQNVQLPREGQEDQGLTKDYGNSPLHRFKKPGSKNFQNIFPPSA
TLHLSNIPPSVSEEDLKVLFSSNGGVVKGFKFFQKDRKMALIQMGSVEEAVQALIDLHNH
DLGENHHLRVSFSKSTI

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Function
Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre- mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre- mRNA. Represses the splicing of MAPT/Tau exon 10. Binds to polypyrimidine-rich controlling element (PCE) of CFTR and promotes exon skipping of CFTR exon 9, thereby antagonizing TIA1 and its role in exon inclusion of CFTR exon 9. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to a polypyrimidine tract flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. In case of infection by picornaviruses, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES- mediated translation. { | , | , | , | , | , | , | , | }.

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HGNC ID
HGNC:9583
KEGG ID hsa:5725
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PTBP1 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 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 Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
A total of eight male BALB/c nude mice (4-5 weeks old; weight, 13-18 g) were obtained from Beijing Vital River Laboratories. The mice were randomly divided into the following two groups: The NC + SF and sh-PTBP1 + SF groups. Hep3B cells (2 x 106) were subcutaneously injected into the right flank of each mouse. The mice were injected intraperitoneally with SF (10 mg/kg) every 2 days for 2 weeks.

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Response regulation PTBP1 mediates ferroptosis in liver cancer cells by regulating NCOA4 translation.In vivoexperiments reconfirmed the role of the PTBP1NCOA4axis in a xenograft transplantation model. It was observed that the mean tumor weight increased afterPTBP1knockout.
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 [2]
Target for Ferroptosis Driver
Responsed Disease Lung injury ICD-11: NB32
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mLVECs (Mouse lung microvascular endothelial cells)
In Vivo Model
The sepsis mouse model was established by cecal ligation and puncture (CLP) of male C57BL/6 mouse (6-8 weeks, Guangzhou Animal Medical Center). Firstly, the mice were anesthetized by intraperitoneal injection of 4% chloral hydrate (0.1 ml/10g). The cecum was found by cutting a 1 cm longitudinally in the abdomen of the mice, and ligating the cecum from the end of the cecum to half the length of the ileocecal valve with 5-0 silk suture. Then a 21 G needle was used to puncture the ligature and the midpoint of the cecum once, and finally the wound was sutured. In the sham operation group, only laparotomy was performed, without ligation and perforation of the cecum. All animal-related experiments in this study were approved by hospital ethics committee according to following the Nation Institutes of Health Guide for the Laboratory Animals Care and Use (approval No. Med-Eth-Re [2022] 168).

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Response regulation CircEXOC5 can enhance the stability of the target gene ACSL4 by binding to the RNA binding protein PTBP1 and up-regulate its expression, thereby promoting ferroptosis and exacerbating sepsis-induced acute lung injury.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Polypyrimidine tract-binding protein 1 (PTBP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
A total of eight male BALB/c nude mice (4-5 weeks old; weight, 13-18 g) were obtained from Beijing Vital River Laboratories. The mice were randomly divided into the following two groups: The NC + SF and sh-PTBP1 + SF groups. Hep3B cells (2 x 106) were subcutaneously injected into the right flank of each mouse. The mice were injected intraperitoneally with SF (10 mg/kg) every 2 days for 2 weeks.

    Click to Show/Hide
Response regulation PTBP1 mediates ferroptosis in liver cancer cells by regulating NCOA4 translation.In vivoexperiments reconfirmed the role of the PTBP1NCOA4axis in a xenograft transplantation model. It was observed that the mean tumor weight increased afterPTBP1knockout.
Lung injury [ICD-11: NB32]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Polypyrimidine tract-binding protein 1 (PTBP1) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mLVECs (Mouse lung microvascular endothelial cells)
In Vivo Model
The sepsis mouse model was established by cecal ligation and puncture (CLP) of male C57BL/6 mouse (6-8 weeks, Guangzhou Animal Medical Center). Firstly, the mice were anesthetized by intraperitoneal injection of 4% chloral hydrate (0.1 ml/10g). The cecum was found by cutting a 1 cm longitudinally in the abdomen of the mice, and ligating the cecum from the end of the cecum to half the length of the ileocecal valve with 5-0 silk suture. Then a 21 G needle was used to puncture the ligature and the midpoint of the cecum once, and finally the wound was sutured. In the sham operation group, only laparotomy was performed, without ligation and perforation of the cecum. All animal-related experiments in this study were approved by hospital ethics committee according to following the Nation Institutes of Health Guide for the Laboratory Animals Care and Use (approval No. Med-Eth-Re [2022] 168).

    Click to Show/Hide
Response regulation CircEXOC5 can enhance the stability of the target gene ACSL4 by binding to the RNA binding protein PTBP1 and up-regulate its expression, thereby promoting ferroptosis and exacerbating sepsis-induced acute lung injury.
References
Ref 1 The PTBP1NCOA4 axis promotes ferroptosis in liver cancer cells. Oncol Rep. 2023 Feb;49(2):45. doi: 10.3892/or.2023.8482. Epub 2023 Jan 20.
Ref 2 CircEXOC5 promotes ferroptosis by enhancing ACSL4 mRNA stability via binding to PTBP1 in sepsis-induced acute lung injury. Immunobiology. 2022 Jul;227(4):152219. doi: 10.1016/j.imbio.2022.152219. Epub 2022 Apr 12.