Molecule Information

General Information of the Molecule (ID: Mol04423)

• Name: CDGSH iron-sulfur domain-containing protein 2 (CISD2) ,Homo sapiens
• Synonyms: Endoplasmic reticulum intermembrane small protein; MitoNEET-related 1 protein; Nutrient-deprivation autophagy factor-1
• Molecule Type: Protein
• Gene Name: CISD2
• Gene ID: 493856
• Sequence:
  MVLESVARIVKVQLPAYLKRLPVPESITGFARLTVSEWLRLLPFLGVLALLGYLAVRPFL
  PKKKQQKDSLINLKIQKENPKVVNEINIEDLCLTKAAYCRCWRSKTFPACDGSHNKHNE
  L TGDNVGPLILKKKEV
• Function: Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participatesin the interaction of BCL2 with BECN1 and is required for BCL2-mediateddepression of endoplasmic reticulum Ca stores during autophagy.Contributes to BIK-initiated autophagy, while it is not involved inBIK-dependent activation of caspases. Involved in life span control,probably via its function as regulator of autophagy.{ECO:0000269|PubMed:17846994, ECO:0000269|PubMed:20010695}.
• Uniprot ID: CISD2_HUMAN
• Ensembl ID: ENSG0000014535412
• HGNC ID: HGNC:24212

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Diffuse large B-cell lymphoma [ICD-11: 2A81.0] [1]

• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HBL-1/DOX cells; Lymph; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay; qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Cell proliferation assay
• Mechanism Description: CISD2 may play a role in promoting tumor cell proliferation and drug resistance through ferroptosis and ferritinophagy. CISD2 expression levels were higher in HBL-1/DOX cells compared to HBL-1 cells.

Patented Agent(s) 1 drug(s) in total

Erastin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Diffuse large B-cell lymphoma [ICD-11: 2A81.0] [1]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Sensitive Drug: Erastin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HBL-1/DOX cells; Lymph; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: CCK8 assay; Cell proliferation assay
• Mechanism Description: A decrease in cell proliferation was observed in HBL-1/DOX cells transfected with shCISD2 and treated with 10 µM Erastin, compared to the inhibition of shCISD2 in HBL-1/DOX cells . Additionally, increases in iron , MDA , and ROS generation were induced by Erastin , while decreases in GSH and MMPs were also observed. Treatment of HBL-1/DOX cells with a combination of Erastin and shCISD2 resulted in a decrease in CISD2, p62, FTH1, and GPX4 levels, along with an increase in BECN1 and NCOA4. These findings suggest that inhibiting CISD2 can enhance the effects of Erastin by promoting increased ferroptosis and ferritinophagy, thereby contributing to the cell death of HBL-1/DOX cells.

References

• Ref 1: Inhibition of CISD2 enhances sensitivity to doxorubicin in diffuse large B-cell lymphoma by regulating ferroptosis and ferritinophagy. Front Pharmacol. 2024 Nov 13;15:1482354.