General Information of the Ferroptosis Regulator (ID: REG10467)
Regulator Name Ubiquitin carboxyl-terminal hydrolase 14 (USP14)
Synonyms
TGT; Deubiquitinating enzyme 14; Ubiquitin thioesterase 14; Ubiquitin-specific-processing protease 14
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Gene Name USP14
Gene ID 9097
Regulator Type Protein coding
Uniprot ID P54578
Sequence
MPLYSVTVKWGKEKFEGVELNTDEPPMVFKAQLFALTGVQPARQKVMVKGGTLKDDDWGN
IKIKNGMTLLMMGSADALPEEPSAKTVFVEDMTEEQLASAMELPCGLTNLGNTCYMNATV
QCIRSVPELKDALKRYAGALRASGEMASAQYITAALRDLFDSMDKTSSSIPPIILLQFLH
MAFPQFAEKGEQGQYLQQDANECWIQMMRVLQQKLEAIEDDSVKETDSSSASAATPSKKK
SLIDQFFGVEFETTMKCTESEEEEVTKGKENQLQLSCFINQEVKYLFTGLKLRLQEEITK
QSPTLQRNALYIKSSKISRLPAYLTIQMVRFFYKEKESVNAKVLKDVKFPLMLDMYELCT
PELQEKMVSFRSKFKDLEDKKVNQQPNTSDKKSSPQKEVKYEPFSFADDIGSNNCGYYDL
QAVLTHQGRSSSSGHYVSWVKRKQDEWIKFDDDKVSIVTPEDILRLSGGGDWHIAYVLLY
GPRRVEIMEEESEQ

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Family Peptidase C19 family
Function
Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non- stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs) (By similarity). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation.

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HGNC ID
HGNC:12612
KEGG ID hsa:9097
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
USP14 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 Lung cancer ICD-11: 2C25
Responsed Drug Gingerol Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
BALB/cNude (6-8 weeks of age) mice were purchased from Hangzhou Ziyuan Experimental Animal Technology Co. Ltd. (SYXK-20180049) for this study. The mice were housed under specific pathogen-free conditions at 23 and given free access to food and water. The left flank of mice was subcutaneously inoculated with A549 tumor-cell suspension (5 x 106 cells/100uL) to prepare A549 tumor xenografts. Three days after tumor cell inoculation, the mice were divided into three groups (n = 8): Con group (control group, no treatment), L-Gin group (0.25 mg/kg/day 6-Gingerol), H-Gin group (0.5 mg/kg/day 6-Gingerol), which were administered orally daily until the end of the experiments. Mice were killed when their minor axis of tumors were longer than 20 mm.

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Response regulation 6-Gingerol inhibits lung cancer cell growth via suppression of USP14 expression and its downstream regulation of autophagy-dependent ferroptosis, revealing the function and efficacy of 6-Gingerol as a therapeutic compound in A549 and its possible mechanism of action.
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Ubiquitin carboxyl-terminal hydrolase 14 (USP14) Protein coding
Responsed Drug Gingerol Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
BALB/cNude (6-8 weeks of age) mice were purchased from Hangzhou Ziyuan Experimental Animal Technology Co. Ltd. (SYXK-20180049) for this study. The mice were housed under specific pathogen-free conditions at 23 and given free access to food and water. The left flank of mice was subcutaneously inoculated with A549 tumor-cell suspension (5 x 106 cells/100uL) to prepare A549 tumor xenografts. Three days after tumor cell inoculation, the mice were divided into three groups (n = 8): Con group (control group, no treatment), L-Gin group (0.25 mg/kg/day 6-Gingerol), H-Gin group (0.5 mg/kg/day 6-Gingerol), which were administered orally daily until the end of the experiments. Mice were killed when their minor axis of tumors were longer than 20 mm.

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Response regulation 6-Gingerol inhibits lung cancer cell growth via suppression of USP14 expression and its downstream regulation of autophagy-dependent ferroptosis, revealing the function and efficacy of 6-Gingerol as a therapeutic compound in A549 and its possible mechanism of action.
Gingerol [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Lung cancer ICD-11: 2C25
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
In Vivo Model
BALB/cNude (6-8 weeks of age) mice were purchased from Hangzhou Ziyuan Experimental Animal Technology Co. Ltd. (SYXK-20180049) for this study. The mice were housed under specific pathogen-free conditions at 23 and given free access to food and water. The left flank of mice was subcutaneously inoculated with A549 tumor-cell suspension (5 x 106 cells/100uL) to prepare A549 tumor xenografts. Three days after tumor cell inoculation, the mice were divided into three groups (n = 8): Con group (control group, no treatment), L-Gin group (0.25 mg/kg/day 6-Gingerol), H-Gin group (0.5 mg/kg/day 6-Gingerol), which were administered orally daily until the end of the experiments. Mice were killed when their minor axis of tumors were longer than 20 mm.

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Response regulation 6-Gingerol inhibits lung cancer cell growth via suppression of USP14 expression and its downstream regulation of autophagy-dependent ferroptosis, revealing the function and efficacy of 6-Gingerol as a therapeutic compound in A549 and its possible mechanism of action.
References
Ref 1 The Inhibitory Effect of 6-Gingerol on Ubiquitin-Specific Peptidase 14 Enhances Autophagy-Dependent Ferroptosis and Anti-Tumor in vivo and in vitro. Front Pharmacol. 2020 Nov 13;11:598555. doi: 10.3389/fphar.2020.598555. eCollection 2020.