Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10012)
Regulator Name 26S proteasome non-ATPase regulatory subunit 14 (PSMD14)
Synonyms
POH1; 26S proteasome regulatory subunit RPN11; 26S proteasome-associated PAD1 homolog 1
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Gene Name PSMD14
Gene ID 10213
Regulator Type Protein coding
Uniprot ID O00487
Sequence
MDRLLRLGGGMPGLGQGPPTDAPAVDTAEQVYISSLALLKMLKHGRAGVPMEVMGLMLGE
FVDDYTVRVIDVFAMPQSGTGVSVEAVDPVFQAKMLDMLKQTGRPEMVVGWYHSHPGFGC
WLSGVDINTQQSFEALSERAVAVVVDPIQSVKGKVVIDAFRLINANMMVLGHEPRQTTSN
LGHLNKPSIQALIHGLNRHYYSITINYRKNELEQKMLLNLHKKSWMEGLTLQDYSEHCKH
NESVVKEMLELAKNYNKAVEEEDKMTPEQLAIKNVGKQDPKRHLEEHVDVLMTSNIVQCL
AAMLDTVVFK

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Family Peptidase M67A family
Function
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading.

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HGNC ID
HGNC:16889
KEGG ID hsa:10213
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PSMD14 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
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 T24 cells Bladder carcinoma Homo sapiens CVCL_0554
5637 cells Bladder carcinoma Homo sapiens CVCL_0126
J82 cells Bladder carcinoma Homo sapiens CVCL_0359
UM-UC-3 cells Bladder carcinoma Homo sapiens CVCL_1783
In Vivo Model
Twenty female BALB/c nude mice (4-6-weeks old, 15 g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). All mice were housed under specific pathogen-free conditions in 12/12 cycle of light at room temperature (24-26 ). Mice were fed a full fat diet and autoclaved water. The number of mice did not exceed five per cage. A total of 1 x 107 infected 5637 cells were suspended in 100 uL PBS and injected into the shoulder of the mice. Tumor length (L) and width (W) were observed for 4 weeks. Tumor volume (V) was monitored by measuring the length and width of the tumor using the following equation: V = (L x W2) x 0.5. The mice were euthanized by cervical dislocation after inhalational of CO2 when the maximum diameter of any tumor was near 1.5 cm. Tumor tissues were excised and embedded in paraffin for ematoxylin and eosin (HE) or IHC staining.

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Response regulation PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation and induce ferroptosis of bladder cancer cells through the downregulation of GPX4.
Bladder cancer [ICD-11: 2C94]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 T24 cells Bladder carcinoma Homo sapiens CVCL_0554
5637 cells Bladder carcinoma Homo sapiens CVCL_0126
J82 cells Bladder carcinoma Homo sapiens CVCL_0359
UM-UC-3 cells Bladder carcinoma Homo sapiens CVCL_1783
In Vivo Model
Twenty female BALB/c nude mice (4-6-weeks old, 15 g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). All mice were housed under specific pathogen-free conditions in 12/12 cycle of light at room temperature (24-26 ). Mice were fed a full fat diet and autoclaved water. The number of mice did not exceed five per cage. A total of 1 x 107 infected 5637 cells were suspended in 100 uL PBS and injected into the shoulder of the mice. Tumor length (L) and width (W) were observed for 4 weeks. Tumor volume (V) was monitored by measuring the length and width of the tumor using the following equation: V = (L x W2) x 0.5. The mice were euthanized by cervical dislocation after inhalational of CO2 when the maximum diameter of any tumor was near 1.5 cm. Tumor tissues were excised and embedded in paraffin for ematoxylin and eosin (HE) or IHC staining.

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Response regulation PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation and induce ferroptosis of bladder cancer cells through the downregulation of GPX4.
References
Ref 1 Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4. PeerJ. 2023 Jan 6;11:e14654. doi: 10.7717/peerj.14654. eCollection 2023.