Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10274)
Regulator Name Protein mono-ADP-ribosyltransferase PARP16
Synonyms
ADP-ribosyltransferase diphtheria toxin-like 15
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Gene ID 54956
Regulator Type Protein coding
Uniprot ID Q8N5Y8
Sequence
MQPSGWAAAREAAGRDMLAADLRCSLFASALQSYKRDSVLRPFPASYARGDCKDFEALLA
DASKLPNLKELLQSSGDNHKRAWDLVSWILSSKVLTIHSAGKAEFEKIQKLTGAPHTPVP
APDFLFEIEYFDPANAKFYETKGERDLIYAFHGSRLENFHSIIHNGLHCHLNKTSLFGEG
TYLTSDLSLALIYSPHGHGWQHSLLGPILSCVAVCEVIDHPDVKCQTKKKDSKEIDRRRA
RIKHSEGGDIPPKYFVVTNNQLLRVKYLLVYSQKPPKRASSQLSWFSSHWFTVMISLYLL
LLLIVSVINSSAFQHFWNRAKR

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Family ARTD/PARP family
Function
Intracellular mono-ADP-ribosyltransferase that plays a role in different processes, such as protein translation and unfolded protein response (UPR), through the mono-ADP-ribosylation of proteins involved in those processes. Acts as an inhibitor of protein translation by catalyzing mono-ADP-ribosylation of ribosomal subunits, such as RPL14 and RPS6, thereby inhibiting polysome assembly and mRNA loading. Mono-ADP-ribosylation of ribosomal subunits is promoted by NMNAT2. Involved in the unfolded protein response (UPR) by ADP-ribosylating and activating EIF2AK3 and ERN1, two important UPR effectors. May also mediate mono-ADP-ribosylation of karyopherin KPNB1 a nuclear import factor. May not modify proteins on arginine or cysteine residues compared to other mono-ADP-ribosyltransferases.

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HGNC ID
HGNC:26040
KEGG ID hsa:54956
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
Protein mono-ADP-ribosyltransferase PARP16 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
Cystine/glutamate transporter (SLC7A11) [Driver; 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 Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model
 HEY cells Ovarian carcinoma Homo sapiens CVCL_0297
A2780 cells Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures.

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Response regulation Mechanistically, pharmacological inhibition or genetic deletion of PARP16 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP16 is the primary therapeutic strategy for BRCA mutant ovarian cancer.
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Protein mono-ADP-ribosyltransferase PARP16 Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model
 HEY cells Ovarian carcinoma Homo sapiens CVCL_0297
A2780 cells Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
SK-OV-3 cells Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures.

    Click to Show/Hide
Response regulation Mechanistically, pharmacological inhibition or genetic deletion of PARP16 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP16 is the primary therapeutic strategy for BRCA mutant ovarian cancer.
References
Ref 1 PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer. Redox Biol. 2021 Jun;42:101928. doi: 10.1016/j.redox.2021.101928. Epub 2021 Mar 5.