Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10339)
Regulator Name Tumor protein 63 (TP63)
Synonyms
KET, P63, P73H, P73L, TP73L; Chronic ulcerative stomatitis protein; Keratinocyte transcription factor KET; Transformation-related protein 63; Tumor protein p73-like; p40; p51
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Gene Name TP63
Gene ID 8626
Regulator Type Protein coding
Uniprot ID Q9H3D4
Sequence
MNFETSRCATLQYCPDPYIQRFVETPAHFSWKESYYRSTMSQSTQTNEFLSPEVFQHIWD
FLEQPICSVQPIDLNFVDEPSEDGATNKIEISMDCIRMQDSDLSDPMWPQYTNLGLLNSM
DQQIQNGSSSTSPYNTDHAQNSVTAPSPYAQPSSTFDALSPSPAIPSNTDYPGPHSFDVS
FQQSSTAKSATWTYSTELKKLYCQIAKTCPIQIKVMTPPPQGAVIRAMPVYKKAEHVTEV
VKRCPNHELSREFNEGQIAPPSHLIRVEGNSHAQYVEDPITGRQSVLVPYEPPQVGTEFT
TVLYNFMCNSSCVGGMNRRPILIIVTLETRDGQVLGRRCFEARICACPGRDRKADEDSIR
KQQVSDSTKNGDGTKRPFRQNTHGIQMTSIKKRRSPDDELLYLPVRGRETYEMLLKIKES
LELMQYLPQHTIETYRQQQQQQHQHLLQKQTSIQSPSSYGNSSPPLNKMNSMNKLPSVSQ
LINPQQRNALTPTTIPDGMGANIPMMGTHMPMAGDMNGLSPTQALPPPLSMPSTSHCTPP
PPYPTDCSIVSFLARLGCSSCLDYFTTQGLTTIYQIEHYSMDDLASLKIPEQFRHAIWKG
ILDHRQLHEFSSPSHLLRTPSSASTVSVGSSETRGERVIDAVRFTLRQTISFPPRDEWND
FNFDMDARRNKQQRIKEEGE

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Family P53 family
Function
Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.

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HGNC ID
HGNC:15979
KEGG ID hsa:8626
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TP63 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
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
OVCAR5 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_1628
COV362 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_2420
FT190 cells Normal Homo sapiens CVCL_UH57
PEO1 cells Metastasis of ovarian carcinoma Homo sapiens CVCL_2686
PEO4 cells Ovarian cystadenocarcinoma Homo sapiens CVCL_2690
In Vivo Model
To develop platinum resistant OC cells in vivo, female (6-8 weeks old) athymic nude mice (Foxn1nu, Envigo) were injected subcutaneously (s.c.) with 2 million SKOV3 or OVCAR3 cells, or intraperitoneally (i.p.) with 2 million OVCAR5 cells to induce tumors.

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Response regulation Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7 platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors.
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Tumor protein 63 (TP63) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
OVCAR-3 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
OVCAR5 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_1628
COV362 cells Ovarian serous adenocarcinoma Homo sapiens CVCL_2420
FT190 cells Normal Homo sapiens CVCL_UH57
PEO1 cells Metastasis of ovarian carcinoma Homo sapiens CVCL_2686
PEO4 cells Ovarian cystadenocarcinoma Homo sapiens CVCL_2690
In Vivo Model
To develop platinum resistant OC cells in vivo, female (6-8 weeks old) athymic nude mice (Foxn1nu, Envigo) were injected subcutaneously (s.c.) with 2 million SKOV3 or OVCAR3 cells, or intraperitoneally (i.p.) with 2 million OVCAR5 cells to induce tumors.

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Response regulation Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7 platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors.
References
Ref 1 Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis. Cancer Res. 2021 Jan 15;81(2):384-399. doi: 10.1158/0008-5472.CAN-20-1488. Epub 2020 Nov 10.