General Information of the Ferroptosis Regulator (ID: REG10263)
Regulator Name L-seryl-tRNA(Sec) kinase (PSTK)
Synonyms
C10orf89; O-phosphoseryl-tRNA(Sec) kinase
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Gene Name PSTK
Gene ID 118672
Regulator Type Protein coding
Uniprot ID Q8IV42
Sequence
MKTAENIRGTGSDGPRKRGLCVLCGLPAAGKSTFARALAHRLQQEQGWAIGVVAYDDVMP
DAFLAGARARPAPSQWKLLRQELLKYLEYFLMAVINGCQMSVPPNRTEAMWEDFITCLKD
QDLIFSAAFEAQSCYLLTKTAVSRPLFLVLDDNFYYQSMRYEVYQLARKYSLGFCQLFLD
CPLETCLQRNGQRPQALPPETIHLMGRKLEKPNPEKNAWEHNSLTIPSPACASEASLEVT
DLLLTALENPVKYAEDNMEQKDTDRIICSTNILHKTDQTLRRIVSQTMKEAKGNQEAFSE
MTFKQRWVRANHAAIWRIILGNEHIKCRSAKVGWLQCCRIEKRPLSTG

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Family L-seryl-tRNA(Sec) kinase family
Function
Specifically phosphorylates seryl-tRNA(Sec) to O- phosphoseryl-tRNA(Sec), an activated intermediate for selenocysteine biosynthesis.

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HGNC ID
HGNC:28578
KEGG ID hsa:118672
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PSTK 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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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
Responsed Drug Punicalin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SNU-387 cells Hepatocellular carcinoma Homo sapiens CVCL_0250
SNU-182 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0090
SNU-398 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0077
WRL 68 cells Endocervical adenocarcinoma Homo sapiens CVCL_0581
HUVECs (Human umbilical vein endothelial cells)
JHH-2 cells Adult hepatocellular carcinoma Homo sapiens CVCL_2786
JHH-7 cells Adult hepatocellular carcinoma Homo sapiens CVCL_2805
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Li-7 cells Adult hepatocellular carcinoma Homo sapiens CVCL_3840
In Vivo Model
Female Nod-SCID mice of 6-8 weeks old were purchased from HFK BIOSCIENCE (Beijing). Hep3B-vehicle/Hep3B-PSTK-KO cells were harvested and injected subcutaneously (1 x 107 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into four groups and injected intraperitoneally with Abemaciclib (50 mg/kg, every other day) or vehicle. Mice were sacrificed when the tumor volume exceeded 2000 mm3. PSTK-KO or vehicle Hep3B cells were implanted and treated with Sorafenib (50 mg/kg, every other day) or Erastin (50 mg/kg, every other day) for 42 days. Tumor volumes were monitored and quantified by the modified ellipsoidal formula, tumor volume = (length x width2)/2. To check the efficacities and appraisal the side effects of PSTK inhibitors, Hep3B cells were harvested and in injected subcutaneously (5 x 106 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into six groups and intragastrically treated with Punicalin (100 mg/kg, every day), Geraniin (100 mg/kg, every day), Sorafenib (50 mg/kg, every day) with or without PSTK inhibitors (Punicalin/Geraniin) for 30 days. Tumor volumes and mice weights were measured every three days.

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Response regulation The depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat Hepatocellular carcinoma in vitro and in vivo.
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator L-seryl-tRNA(Sec) kinase (PSTK) Protein coding
Responsed Drug Punicalin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SNU-387 cells Hepatocellular carcinoma Homo sapiens CVCL_0250
SNU-182 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0090
SNU-398 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0077
WRL 68 cells Endocervical adenocarcinoma Homo sapiens CVCL_0581
HUVECs (Human umbilical vein endothelial cells)
JHH-2 cells Adult hepatocellular carcinoma Homo sapiens CVCL_2786
JHH-7 cells Adult hepatocellular carcinoma Homo sapiens CVCL_2805
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Li-7 cells Adult hepatocellular carcinoma Homo sapiens CVCL_3840
In Vivo Model
Female Nod-SCID mice of 6-8 weeks old were purchased from HFK BIOSCIENCE (Beijing). Hep3B-vehicle/Hep3B-PSTK-KO cells were harvested and injected subcutaneously (1 x 107 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into four groups and injected intraperitoneally with Abemaciclib (50 mg/kg, every other day) or vehicle. Mice were sacrificed when the tumor volume exceeded 2000 mm3. PSTK-KO or vehicle Hep3B cells were implanted and treated with Sorafenib (50 mg/kg, every other day) or Erastin (50 mg/kg, every other day) for 42 days. Tumor volumes were monitored and quantified by the modified ellipsoidal formula, tumor volume = (length x width2)/2. To check the efficacities and appraisal the side effects of PSTK inhibitors, Hep3B cells were harvested and in injected subcutaneously (5 x 106 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into six groups and intragastrically treated with Punicalin (100 mg/kg, every day), Geraniin (100 mg/kg, every day), Sorafenib (50 mg/kg, every day) with or without PSTK inhibitors (Punicalin/Geraniin) for 30 days. Tumor volumes and mice weights were measured every three days.

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Response regulation The depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat Hepatocellular carcinoma in vitro and in vivo.
Punicalin [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_0485
SNU-387 cells Hepatocellular carcinoma Homo sapiens CVCL_0250
SNU-182 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0090
SNU-398 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0077
WRL 68 cells Endocervical adenocarcinoma Homo sapiens CVCL_0581
HUVECs (Human umbilical vein endothelial cells)
JHH-2 cells Adult hepatocellular carcinoma Homo sapiens CVCL_2786
JHH-7 cells Adult hepatocellular carcinoma Homo sapiens CVCL_2805
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Li-7 cells Adult hepatocellular carcinoma Homo sapiens CVCL_3840
In Vivo Model
Female Nod-SCID mice of 6-8 weeks old were purchased from HFK BIOSCIENCE (Beijing). Hep3B-vehicle/Hep3B-PSTK-KO cells were harvested and injected subcutaneously (1 x 107 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into four groups and injected intraperitoneally with Abemaciclib (50 mg/kg, every other day) or vehicle. Mice were sacrificed when the tumor volume exceeded 2000 mm3. PSTK-KO or vehicle Hep3B cells were implanted and treated with Sorafenib (50 mg/kg, every other day) or Erastin (50 mg/kg, every other day) for 42 days. Tumor volumes were monitored and quantified by the modified ellipsoidal formula, tumor volume = (length x width2)/2. To check the efficacities and appraisal the side effects of PSTK inhibitors, Hep3B cells were harvested and in injected subcutaneously (5 x 106 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into six groups and intragastrically treated with Punicalin (100 mg/kg, every day), Geraniin (100 mg/kg, every day), Sorafenib (50 mg/kg, every day) with or without PSTK inhibitors (Punicalin/Geraniin) for 30 days. Tumor volumes and mice weights were measured every three days.

    Click to Show/Hide
Response regulation The depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat Hepatocellular carcinoma in vitro and in vivo.
References
Ref 1 CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma. Mol Cancer. 2022 Jan 4;21(1):11. doi: 10.1186/s12943-021-01466-9.