Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10471)
Regulator Name Transcriptional coactivator YAP1 (YAP1)
Synonyms
YAP65; Protein yorkie homolog; Yes-associated protein YAP65 homolog
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Gene Name YAP1
Gene ID 10413
Regulator Type Protein coding
Uniprot ID P46937
Sequence
MDPGQQPPPQPAPQGQGQPPSQPPQGQGPPSGPGQPAPAATQAAPQAPPAGHQIVHVRGD
SETDLEALFNAVMNPKTANVPQTVPMRLRKLPDSFFKPPEPKSHSRQASTDAGTAGALTP
QHVRAHSSPASLQLGAVSPGTLTPTGVVSGPAATPTAQHLRQSSFEIPDDVPLPAGWEMA
KTSSGQRYFLNHIDQTTTWQDPRKAMLSQMNVTAPTSPPVQQNMMNSASGPLPDGWEQAM
TQDGEIYYINHKNKTTSWLDPRLDPRFAMNQRISQSAPVKQPPPLAPQSPQGGVMGGSNS
NQQQQMRLQQLQMEKERLRLKQQELLRQAMRNINPSTANSPKCQELALRSQLPTLEQDGG
TQNPVSSPGMSQELRTMTTNSSDPFLNSGTYHSRDESTDSGLSMSSYSVPRTPDDFLNSV
DEMDTGDTINQSTLPSQQNRFPDYLEAIPGTNVDLGTLEGDGMNIEGEELMPSLQEALSS
DILNDMESVLAATKLDKESFLTWL

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Family YAP1 family
Function
Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization. Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage- independent growth, and epithelial mesenchymal transition (EMT) induction. Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1. In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity).; [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).; [Isoform 3]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).

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HGNC ID
HGNC:16262
KEGG ID hsa:10413
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
YAP1 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
Transferrin receptor protein 1 (TFRC) [Driver; Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Primary ovarian insufficiency ICD-11: GA30
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

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Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
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 Primary ovarian insufficiency ICD-11: GA30
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

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Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
Ferroptosis suppressor protein 1 (AIFM2) [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 Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 hMPs (Human macrophages)
In Vivo Model
C57BL/6 mice (female, 6-8 weeks old, 20-30 g weight) and SPF-grade SD rats (female, 180-230 g weight) were used to detect the toxicity of nanoparticles. Different cells (5 x 106) cells were grafted in the left flank; 5 days after engraftation, the stimulated TAMs (1 x 106) were injected into NSG mice through the tail vein. Different treatments were given and recorded as day 0.

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Response regulation The NF2- YAP signaling axis modulated the expression of ferroptosis suppressor protein 1 (FSP1) and CD24 in CD24 high cells. This system achieved dual antitumor effects, ultimately promoting cell death and thus inhibiting triple-negative breast cancer (TNBC) tumor growth, with some tumors even disappearing.
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [3]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
SNU-398 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0077
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HLE cells Hepatocellular carcinoma Homo sapiens CVCL_1281
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
In Vivo Model
SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (106 in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks.

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Response regulation In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [4]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model
 Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
HEK-293T cells Normal Homo sapiens CVCL_0063
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
MHCC97-H cells Adult hepatocellular carcinoma Homo sapiens CVCL_4972
HCC-LY10 (Human hepatoma cells)
In Vivo Model
To generate murine subcutaneous tumors, 2 x 106 HCC cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached approximately 100 mm3 at day 15, mice were randomly allocated into groups and treated with erastin or sorafenib for 2 weeks.

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Response regulation Overexpression of AKR1C3 protected against ferroptosis in hepatocellular carcinoma (HCC) cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Transcriptional coactivator YAP1 (YAP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
SNU-398 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0077
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HLE cells Hepatocellular carcinoma Homo sapiens CVCL_1281
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
In Vivo Model
SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (106 in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks.

    Click to Show/Hide
Response regulation In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [4]
Target Regulator Transcriptional coactivator YAP1 (YAP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model
 Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
HEK-293T cells Normal Homo sapiens CVCL_0063
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
MHCC97-H cells Adult hepatocellular carcinoma Homo sapiens CVCL_4972
HCC-LY10 (Human hepatoma cells)
In Vivo Model
To generate murine subcutaneous tumors, 2 x 106 HCC cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached approximately 100 mm3 at day 15, mice were randomly allocated into groups and treated with erastin or sorafenib for 2 weeks.

    Click to Show/Hide
Response regulation Overexpression of AKR1C3 protected against ferroptosis in hepatocellular carcinoma (HCC) cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC.
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Transcriptional coactivator YAP1 (YAP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 hMPs (Human macrophages)
In Vivo Model
C57BL/6 mice (female, 6-8 weeks old, 20-30 g weight) and SPF-grade SD rats (female, 180-230 g weight) were used to detect the toxicity of nanoparticles. Different cells (5 x 106) cells were grafted in the left flank; 5 days after engraftation, the stimulated TAMs (1 x 106) were injected into NSG mice through the tail vein. Different treatments were given and recorded as day 0.

    Click to Show/Hide
Response regulation The NF2- YAP signaling axis modulated the expression of ferroptosis suppressor protein 1 (FSP1) and CD24 in CD24 high cells. This system achieved dual antitumor effects, ultimately promoting cell death and thus inhibiting triple-negative breast cancer (TNBC) tumor growth, with some tumors even disappearing.
Primary ovarian insufficiency [ICD-11: GA30]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcriptional coactivator YAP1 (YAP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

    Click to Show/Hide
Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcriptional coactivator YAP1 (YAP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 ES-2 cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3509
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each.

    Click to Show/Hide
Response regulation Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression.
References
Ref 1 BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency. Nat Commun. 2022 Oct 5;13(1):5871. doi: 10.1038/s41467-022-33323-8.
Ref 2 Targeted Intervention of NF2-YAP Signaling Axis in CD24-Overexpressing Cells Contributes to Encouraging Therapeutic Effects in TNBC. ACS Nano. 2022 Apr 26;16(4):5807-5819. doi: 10.1021/acsnano.1c10921. Epub 2022 Apr 14.
Ref 3 YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis. EMBO Mol Med. 2021 Dec 7;13(12):e14351. doi: 10.15252/emmm.202114351. Epub 2021 Oct 19.
Ref 4 AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway. Mol Carcinog. 2023 Jun;62(6):833-844. doi: 10.1002/mc.23527. Epub 2023 Mar 15.