Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10068)
Regulator Name Interferon gamma (IFNG)
Synonyms
Immune interferon
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Gene Name IFNG
Gene ID 3458
Regulator Type Protein coding
Uniprot ID P01579
Sequence
MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK
EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN
YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ

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Family Type II (or gamma) interferon family
Function
Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation. Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription. Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits. In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading. Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference. Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL. Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation.

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HGNC ID
HGNC:5438
KEGG ID hsa:3458
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
IFNG 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
Cystine/glutamate transporter (SLC7A11) [Driver; 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 Fibrosarcoma ICD-11: 2B53
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
B16-F0 cells Melanoma Mus musculus CVCL_0604
ID8 cells Ovarian cancer Mus musculus CVCL_IU14
In Vivo Model
Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 106 tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 106 luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse.

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Response regulation Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma.
4F2 cell-surface antigen heavy chain (SLC3A2) [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 Fibrosarcoma ICD-11: 2B53
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
B16-F0 cells Melanoma Mus musculus CVCL_0604
ID8 cells Ovarian cancer Mus musculus CVCL_IU14
In Vivo Model
Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 106 tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 106 luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse.

    Click to Show/Hide
Response regulation Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma.
Fibrosarcoma [ICD-11: 2B53]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Interferon gamma (IFNG) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
B16-F0 cells Melanoma Mus musculus CVCL_0604
ID8 cells Ovarian cancer Mus musculus CVCL_IU14
In Vivo Model
Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 106 tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 106 luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse.

    Click to Show/Hide
Response regulation Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Interferon gamma (IFNG) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
B16-F0 cells Melanoma Mus musculus CVCL_0604
ID8 cells Ovarian cancer Mus musculus CVCL_IU14
In Vivo Model
Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 106 tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 106 luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse.

    Click to Show/Hide
Response regulation Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma.
References
Ref 1 CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019 May;569(7755):270-274. doi: 10.1038/s41586-019-1170-y. Epub 2019 May 1.