Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10303)
Regulator Name Charged multivesicular body protein 6 (CHMP6)
Synonyms
VPS20; Chromatin-modifying protein 6; Vacuolar protein sorting-associated protein 20
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Gene Name CHMP6
Gene ID 79643
Regulator Type Protein coding
Uniprot ID Q96FZ7
Sequence
MGNLFGRKKQSRVTEQDKAILQLKQQRDKLRQYQKRIAQQLERERALARQLLRDGRKERA
KLLLKKKRYQEQLLDRTENQISSLEAMVQSIEFTQIEMKVMEGLQFGNECLNKMHQVMSI
EEVERILDETQEAVEYQRQIDELLAGSFTQEDEDAILEELSAITQEQIELPEVPSEPLPE
KIPENVPVKARPRQAELVAAS

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Family SNF7 family
Function
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes.

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HGNC ID
HGNC:25675
KEGG ID hsa:79643
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CHMP6 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 Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 or HepG2 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude or B6 mice. Once the tumors reached 50-70 mm3 at day 7, mice were randomly allocated into groups and treated with (1S-3R)-RSL3 (30 mg/kg; i.p., once every other day) for 2 weeks.

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Response regulation ESCRT III-mediated plasma membrane repair can reduce lipid peroxidation and DAMPs (e.g., HMGB1) during ferroptosis. The accumulation of ESCRT-III subunits (e.g., CHMP5 and CHMP6) in the plasma membrane are increased by classical ferroptosis activators (e.g., erastin and RSL3), which relies on endoplasmic reticulum stress and calcium influx in pancreatic ductal adenocarcinoma cells PANC1.
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Charged multivesicular body protein 6 (CHMP6) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
To generate murine subcutaneous tumors, 5 x 106 PANC1 or HepG2 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude or B6 mice. Once the tumors reached 50-70 mm3 at day 7, mice were randomly allocated into groups and treated with (1S-3R)-RSL3 (30 mg/kg; i.p., once every other day) for 2 weeks.

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Response regulation ESCRT III-mediated plasma membrane repair can reduce lipid peroxidation and DAMPs (e.g., HMGB1) during ferroptosis. The accumulation of ESCRT-III subunits (e.g., CHMP5 and CHMP6) in the plasma membrane are increased by classical ferroptosis activators (e.g., erastin and RSL3), which relies on endoplasmic reticulum stress and calcium influx in pancreatic ductal adenocarcinoma cells PANC1.
References
Ref 1 ESCRT-III-dependent membrane repair blocks ferroptosis. Biochem Biophys Res Commun. 2020 Feb 5;522(2):415-421. doi: 10.1016/j.bbrc.2019.11.110. Epub 2019 Nov 21.