Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10490)
Regulator Name Transcription factor PU.1 (SPI1)
Synonyms
31 kDa-transforming protein
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Gene Name SPI1
Gene ID 6688
Regulator Type Protein coding
Uniprot ID P17947
Sequence
MLQACKMEGFPLVPPPSEDLVPYDTDLYQRQTHEYYPYLSSDGESHSDHYWDFHPHHVHS
EFESFAENNFTELQSVQPPQLQQLYRHMELEQMHVLDTPMVPPHPSLGHQVSYLPRMCLQ
YPSLSPAQPSSDEEEGERQSPPLEVSDGEADGLEPGPGLLPGETGSKKKIRLYQFLLDLL
RSGDMKDSIWWVDKDKGTFQFSSKHKEALAHRWGIQKGNRKKMTYQKMARALRNYGKTGE
VKKVKKKLTYQFSGEVLGRGGLAERRHPPH

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Family ETS family
Function
Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites. Once in open chromatin, can directly control gene expression by binding genetic regulatory elements and can also more broadly influence transcription by recruiting transcription factors, such as interferon regulatory factors (IRFs), to otherwise inaccessible genomic regions. Transcriptionally activates genes important for myeloid and lymphoid lineages, such as CSF1R (By similarity). Transcriptional activation from certain promoters, possibly containing low affinity binding sites, is achieved cooperatively with other transcription factors. FCER1A transactivation is achieved in cooperation with GATA1 (By similarity). May be particularly important for the pro- to pre-B cell transition. Binds (via the ETS domain) onto the purine-rich DNA core sequence 5'-GAGGAA-3', also known as the PU-box. In vitro can bind RNA and interfere with pre-mRNA splicing (By similarity).

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HGNC ID
HGNC:11241
KEGG ID hsa:6688
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SPI1 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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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Oesophageal cancer ICD-11: 2B70
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE30 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
In Vivo Model
A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse).

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Response regulation LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells.
Oesophageal cancer [ICD-11: 2B70]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcription factor PU.1 (SPI1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 TE-1 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1759
KYSE30 cells Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
In Vivo Model
A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse).

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Response regulation LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells.
References
Ref 1 LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2023 Jun;72(6):1835-1851. doi: 10.1007/s00262-022-03364-5. Epub 2023 Jan 23.