Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10326)
Regulator Name DNA replication complex GINS protein SLD5 (GINS4)
Synonyms
SLD5; GINS complex subunit 4
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Gene Name GINS4
Gene ID 84296
Regulator Type Protein coding
Uniprot ID Q9BRT9
Sequence
MTEEVDFLGQDSDGGSEEVVLTPAELIERLEQAWMNEKFAPELLESKPEIVECVMEQLEH
MEENLRRAKREDLKVSIHQMEMERIRYVLSSYLRCRLMKIEKFFPHVLEKEKTRPEGEPS
SLSPEELAFAREFMANTESYLKNVALKHMPPNLQKVDLFRAVPKPDLDSYVFLRVRERQE
NILVEPDTDEQRDYVIDLEKGSQHLIRYKTIAPLVASGAVQLI

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Family GINS4/SLD5 family
Function
Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex is a core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built.

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HGNC ID
HGNC:28226
KEGG ID hsa:84296
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
GINS4 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 Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Cell adhesion molecules hsa04514
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
The 4-wk-old female nude mice used in this study were purchased from Hunan SJA Laboratory Animal Co., Ltd (Changsha). Then, 2 x 106 GINS4 WT or KO A549 cells were injected s.c. into nude mice without matrigel. Tumor size was measured every 2 d with a caliper, and volume of tumor was calculated with the formula: L x W2 x 0.5, for L represents the longest diameter and W means the shortest diameter. Then, 2 x 106 p53 WT and KO A549 cells with shCon or shGINS4 overexpressing were injected s.c. into nude mice without matrigel. When tumors reached 60 to 100 mm3, p53 WT with shGINS4 mice were treated with ferrostatin-1 (S7243, Selleckchem) (20 mg/kg) in 2% DMSO, 50% PEG300, 5% Tween80, and 43% water by daily intraperitoneal injection. Tumors were measured three times a week. Mice were sacrificed and tumors were collected finally. Tumor tissue was made into a single-cell suspension for lipid ROS assay using Tumor Dissociation Kit (Miltenyi Biotec).

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Response regulation GINS4 is a potential oncogene in lung adenocarcinoma (LUAD) that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator DNA replication complex GINS protein SLD5 (GINS4) Protein coding
 Regulator Info 
Pathway Response Cell adhesion molecules hsa04514
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
The 4-wk-old female nude mice used in this study were purchased from Hunan SJA Laboratory Animal Co., Ltd (Changsha). Then, 2 x 106 GINS4 WT or KO A549 cells were injected s.c. into nude mice without matrigel. Tumor size was measured every 2 d with a caliper, and volume of tumor was calculated with the formula: L x W2 x 0.5, for L represents the longest diameter and W means the shortest diameter. Then, 2 x 106 p53 WT and KO A549 cells with shCon or shGINS4 overexpressing were injected s.c. into nude mice without matrigel. When tumors reached 60 to 100 mm3, p53 WT with shGINS4 mice were treated with ferrostatin-1 (S7243, Selleckchem) (20 mg/kg) in 2% DMSO, 50% PEG300, 5% Tween80, and 43% water by daily intraperitoneal injection. Tumors were measured three times a week. Mice were sacrificed and tumors were collected finally. Tumor tissue was made into a single-cell suspension for lipid ROS assay using Tumor Dissociation Kit (Miltenyi Biotec).

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Response regulation GINS4 is a potential oncogene in lung adenocarcinoma (LUAD) that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD.
References
Ref 1 GINS4 suppresses ferroptosis by antagonizing p53 acetylation with Snail. Proc Natl Acad Sci U S A. 2023 Apr 11;120(15):e2219585120. doi: 10.1073/pnas.2219585120. Epub 2023 Apr 5.