Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10014)
Regulator Name Pirin (PIR)
Synonyms
Probable quercetin 2,3-dioxygenase PIR
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Gene Name PIR
Gene ID 8544
Regulator Type Protein coding
Uniprot ID O00625
Sequence
MGSSKKVTLSVLSREQSEGVGARVRRSIGRPELKNLDPFLLFDEFKGGRPGGFPDHPHRG
FETVSYLLEGGSMAHEDFCGHTGKMNPGDLQWMTAGRGILHAEMPCSEEPAHGLQLWVNL
RSSEKMVEPQYQELKSEEIPKPSKDGVTVAVISGEALGIKSKVYTRTPTLYLDFKLDPGA
KHSQPIPKGWTSFIYTISGDVYIGPDDAQQKIEPHHTAVLGEGDSVQVENKDPKRSHFVL
IAGEPLREPVIQHGPFVMNTNEEISQAILDFRNAKNGFERAKTWKSKIGN

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Family Pirin family
Function
Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox- state-dependent manner. May be required for efficient terminal myeloid maturation of hematopoietic cells. Has quercetin 2,3-dioxygenase activity (in vitro).

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HGNC ID
HGNC:30048
KEGG ID hsa:8544
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PIR 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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Browse Disease
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 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
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and treated with IKE (imidazole ketone erastin; 40 mg/kg; i.p., once every other day) for 3 weeks, and then samples were collected and assayed.

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Response regulation Pirin (PIR), an iron-binding nuclear protein, plays a previously unrecognized role in mediating ferroptosis resistance in human pancreatic cancer cells. The depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4.
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Pirin (PIR) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and treated with IKE (imidazole ketone erastin; 40 mg/kg; i.p., once every other day) for 3 weeks, and then samples were collected and assayed.

    Click to Show/Hide
Response regulation Pirin (PIR), an iron-binding nuclear protein, plays a previously unrecognized role in mediating ferroptosis resistance in human pancreatic cancer cells. The depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4.
References
Ref 1 Pirin is a nuclear redox-sensitive modulator of autophagy-dependent ferroptosis. Biochem Biophys Res Commun. 2021 Jan 15;536:100-106. doi: 10.1016/j.bbrc.2020.12.066. Epub 2020 Dec 26.