Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10365)
Regulator Name Ubiquitin carboxyl-terminal hydrolase 35 (USP35)
Synonyms
KIAA1372, USP34; Deubiquitinating enzyme 35; Ubiquitin thioesterase 35; Ubiquitin-specific-processing protease 35
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Gene Name USP35
Gene ID 57558
Regulator Type Protein coding
Uniprot ID Q9P2H5
Sequence
MDKILEAVVTSSYPVSVKQGLVRRVLEAARQPLEREQCLALLALGARLYVGGAEELPRRV
GCQLLHVAGRHHPDVFAEFFSARRVLRLLQGGAGPPGPRALACVQLGLQLLPEGPAADEV
FALLRREVLRTVCERPGPAACAQVARLLARHPRCVPDGPHRLLFCQQLVRCLGRFRCPAE
GEEGAVEFLEQAQQVSGLLAQLWRAQPAAILPCLKELFAVISCAEEEPPSSALASVVQHL
PLELMDGVVRNLSNDDSVTDSQMLTAISRMIDWVSWPLGKNIDKWIIALLKGLAAVKKFS
ILIEVSLTKIEKVFSKLLYPIVRGAALSVLKYMLLTFQHSHEAFHLLLPHIPPMVASLVK
EDSNSGTSCLEQLAELVHCMVFRFPGFPDLYEPVMEAIKDLHVPNEDRIKQLLGQDAWTS
QKSELAGFYPRLMAKSDTGKIGLINLGNTCYVNSILQALFMASDFRHCVLRLTENNSQPL
MTKLQWLFGFLEHSQRPAISPENFLSASWTPWFSPGTQQDCSEYLKYLLDRLHEEEKTGT
RICQKLKQSSSPSPPEEPPAPSSTSVEKMFGGKIVTRICCLCCLNVSSREEAFTDLSLAF
PPPERCRRRRLGSVMRPTEDITARELPPPTSAQGPGRVGPRRQRKHCITEDTPPTSLYIE
GLDSKEAGGQSSQEERIEREEEGKEERTEKEEVGEEEESTRGEGEREKEEEVEEEEEKVE
KETEKEAEQEKEEDSLGAGTHPDAAIPSGERTCGSEGSRSVLDLVNYFLSPEKLTAENRY
YCESCASLQDAEKVVELSQGPCYLILTLLRFSFDLRTMRRRKILDDVSIPLLLRLPLAGG
RGQAYDLCSVVVHSGVSSESGHYYCYAREGAARPAASLGTADRPEPENQWYLFNDTRVSF
SSFESVSNVTSFFPKDTAYVLFYRQRPREGPEAELGSSRVRTEPTLHKDLMEAISKDNIL
YLQEQEKEARSRAAYISALPTSPHWGRGFDEDKDEDEGSPGGCNPAGGNGGDFHRLVF

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Family Peptidase C19 family
HGNC ID
HGNC:20061
KEGG ID hsa:57558
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
USP35 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).
Browse Target
Browse Disease
Solute carrier family 40 member 1 (SLC40A1) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 BEAS-2B cells Normal Homo sapiens CVCL_0168
HBE1 cells Normal Homo sapiens CVCL_0287
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
In Vivo Model
BALB/c nude mice (4-5 weeks old) were obtained from HFK Bioscience Co., Ltd (Beijing, China) and maintained in a SPF barrier system. H460, H1299 or H1650 cell lines at a dose of 1 x 106 with or without USP35 manipulation were subcutaneously injected into the right dorsal flank of the nude mice.

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Response regulation USP35 was abundant in human lung cancer tissues and cell lines. USP35 knockdown promoted ferroptosis, and inhibited cell growth, colony formation, and tumor progression in lung cancer cells. Further studies determined that USP35 directly interacted with ferroportin (FPN) and functioned as a deubiquitinase to maintain its protein stability.
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Hereditary Leiomyomatosis ICD-11: 2C90
 Disease Info 
Pathway Response Ubiquitin mediated proteolysis hsa04120
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
HEK-293T cells Normal Homo sapiens CVCL_0063
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
OS-RC-2 cells Clear cell renal cell carcinoma Homo sapiens CVCL_1626
In Vivo Model
Female Balb/c nude mice aged 6 weeks were obtained from Vital River Laboratory (Beijing, China). To generate xenografts of RCC, mice were randomized into two groups of 8 that were subcutaneously inoculated with 1 x 10^7 of OS-RC-2 cells stably transfected with USP35 Tet-on shRNA constructs or empty vector. After 7 days, mice were administered with doxycycline every day (20 mg/kg) to induce shRNA expression through oral gavage without blinding.

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Response regulation USP35 functions to maintain NRF2 levels by catalyzing its deubiquitylation and thus antagonizing degradation. NRF2 reduction imposed by USP35 silencing rendered renal clear cell carcinoma cells increased sensitivity to ferroptosis induction.
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 Ubiquitin carboxyl-terminal hydrolase 35 (USP35) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 BEAS-2B cells Normal Homo sapiens CVCL_0168
HBE1 cells Normal Homo sapiens CVCL_0287
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
In Vivo Model
BALB/c nude mice (4-5 weeks old) were obtained from HFK Bioscience Co., Ltd (Beijing, China) and maintained in a SPF barrier system. H460, H1299 or H1650 cell lines at a dose of 1 x 106 with or without USP35 manipulation were subcutaneously injected into the right dorsal flank of the nude mice.

    Click to Show/Hide
Response regulation USP35 was abundant in human lung cancer tissues and cell lines. USP35 knockdown promoted ferroptosis, and inhibited cell growth, colony formation, and tumor progression in lung cancer cells. Further studies determined that USP35 directly interacted with ferroportin (FPN) and functioned as a deubiquitinase to maintain its protein stability.
Hereditary Leiomyomatosis [ICD-11: 2C90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Ubiquitin carboxyl-terminal hydrolase 35 (USP35) Protein coding
 Regulator Info 
Pathway Response Ubiquitin mediated proteolysis hsa04120
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model
 786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
HEK-293T cells Normal Homo sapiens CVCL_0063
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
OS-RC-2 cells Clear cell renal cell carcinoma Homo sapiens CVCL_1626
In Vivo Model
Female Balb/c nude mice aged 6 weeks were obtained from Vital River Laboratory (Beijing, China). To generate xenografts of RCC, mice were randomized into two groups of 8 that were subcutaneously inoculated with 1 x 10^7 of OS-RC-2 cells stably transfected with USP35 Tet-on shRNA constructs or empty vector. After 7 days, mice were administered with doxycycline every day (20 mg/kg) to induce shRNA expression through oral gavage without blinding.

    Click to Show/Hide
Response regulation USP35 functions to maintain NRF2 levels by catalyzing its deubiquitylation and thus antagonizing degradation. NRF2 reduction imposed by USP35 silencing rendered renal clear cell carcinoma cells increased sensitivity to ferroptosis induction.
References
Ref 1 Deubiquitinase USP35 modulates ferroptosis in lung cancer via targeting ferroportin. Clin Transl Med. 2021 Apr;11(4):e390. doi: 10.1002/ctm2.390.
Ref 2 The deubiquitylating enzyme USP35 restricts regulated cell death to promote survival of renal clear cell carcinoma. Cell Death Differ. 2023 Jul;30(7):1757-1770. doi: 10.1038/s41418-023-01176-3. Epub 2023 May 12.