Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10485)
Regulator Name NF-kappa-B inhibitor alpha (NFKBIA)
Synonyms
IKBA; MAD3; NFKBI; I-kappa-B-alpha; Major histocompatibility complex enhancer-binding protein MAD3
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Gene Name NFKBIA
Gene ID 4792
Regulator Type Protein coding
Uniprot ID P25963
Sequence
MFQAAERPQEWAMEGPRDGLKKERLLDDRHDSGLDSMKDEEYEQMVKELQEIRLEPQEVP
RGSEPWKQQLTEDGDSFLHLAIIHEEKALTMEVIRQVKGDLAFLNFQNNLQQTPLHLAVI
TNQPEIAEALLGAGCDPELRDFRGNTPLHLACEQGCLASVGVLTQSCTTPHLHSILKATN
YNGHTCLHLASIHGYLGIVELLVSLGADVNAQEPCNGRTALHLAVDLQNPDLVSLLLKCG
ADVNRVTYQGYSPYQLTWGRPSTRIQQQLGQLTLENLQMLPESEDEESYDTESEFTEFTE
DELPYDDCVFGGQRLTL

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Family NF-kappa-B inhibitor family
Function
Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals. On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.

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HGNC ID
HGNC:7797
KEGG ID hsa:4792
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
NFKBIA 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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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 Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Drug RSL3 Investigative
 Drug Info 
Pathway Response NF-kappa B signaling pathway hsa04064
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 106 U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm3, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks.

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Response regulation NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11.
Glioblastoma [ICD-11: 2A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator NF-kappa-B inhibitor alpha (NFKBIA) Protein coding
 Regulator Info 
Responsed Drug RSL3 Investigative
 Drug Info 
Pathway Response NF-kappa B signaling pathway hsa04064
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 106 U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm3, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks.

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Response regulation NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11.
RSL3 [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Cystine/glutamate transporter (SLC7A11) Driver; Suppressor
 Target Info 
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response NF-kappa B signaling pathway hsa04064
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 106 U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm3, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks.

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Response regulation NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11.
References
Ref 1 RSL3 Drives Ferroptosis through NF-B Pathway Activation and GPX4 Depletion in Glioblastoma. Oxid Med Cell Longev. 2021 Dec 26;2021:2915019. doi: 10.1155/2021/2915019. eCollection 2021.