Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10019)
Target Name CDGSH iron-sulfur domain-containing protein 2 (CISD2)
Synonyms
Endoplasmic reticulum intermembrane small protein; MitoNEET-related 1 protein; Nutrient-deprivation autophagy factor-1
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Gene Name CISD2
Sequence
MVLESVARIVKVQLPAYLKRLPVPESITGFARLTVSEWLRLLPFLGVLALLGYLAVRPFL
PKKKQQKDSLINLKIQKENPKVVNEINIEDLCLTKAAYCRCWRSKTFPACDGSHNKHNEL
TGDNVGPLILKKKEV

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Family CISD protein family
Function
Regulator of autophagy that contributes to antagonize BECN1- mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.

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Gene ID 493856
Uniprot ID
Q8N5K1
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
CISD2 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Unspecific Regulator
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
Response Description Inhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant hepatocellular carcinoma (HCC).
Head neck squamous cell carcinoma [ICD-11: 2D60]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 AMC-HN-2 cells Hypopharyngeal squamous cell carcinoma Homo sapiens CVCL_5960
SNU-1041 cells Hypopharyngeal squamous cell carcinoma Homo sapiens CVCL_L085
SNU-1066 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5005
SNU-1076 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5006
In Vivo Model
Six-week-old athymic BALB/c malenude mice(nu/nu) were purchased from the Central Lab Animal Inc. (Seoul, Republic of Korea). SAS-resistant HN10 cells were injected subcutaneously into the flank of nude mice. Following the detection of gross nodules from the tumor implants, the mice were subjected to four different treatments: vehicle, SAS (250mg/kg daily per intraperitoneal route), PGZ (20 mg/kg daily per oral administration), or SAS plus PGZ.

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Response Description CISD2 inhibition overcomes head and neck cancer (HNC) resistance to ferroptotic cell death induced by sulfasalazine via increased accumulation of mitochondrial ferrous iron and lipid ROS.
References
Ref 1 CISD2 Promotes Resistance to Sorafenib-Induced Ferroptosis by Regulating Autophagy in Hepatocellular Carcinoma. Front Oncol. 2021 Aug 16;11:657723. doi: 10.3389/fonc.2021.657723. eCollection 2021.
Ref 2 CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer. Cancer Lett. 2018 Sep 28;432:180-190. doi: 10.1016/j.canlet.2018.06.018. Epub 2018 Jun 18.