Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10379)
Regulator Name Protein mono-ADP-ribosyltransferase PARP3 (PARP3)
Synonyms
ADP-ribosyltransferase diphtheria toxin-like 3
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Gene Name PARP3
Gene ID 10039
Regulator Type Protein coding
Uniprot ID Q9Y6F1
Sequence
MAPKPKPWVQTEGPEKKKGRQAGREEDPFRSTAEALKAIPAEKRIIRVDPTCPLSSNPGT
QVYEDYNCTLNQTNIENNNNKFYIIQLLQDSNRFFTCWNRWGRVGEVGQSKINHFTRLED
AKKDFEKKFREKTKNNWAERDHFVSHPGKYTLIEVQAEDEAQEAVVKVDRGPVRTVTKRV
QPCSLDPATQKLITNIFSKEMFKNTMALMDLDVKKMPLGKLSKQQIARGFEALEALEEAL
KGPTDGGQSLEELSSHFYTVIPHNFGHSQPPPINSPELLQAKKDMLLVLADIELAQALQA
VSEQEKTVEEVPHPLDRDYQLLKCQLQLLDSGAPEYKVIQTYLEQTGSNHRCPTLQHIWK
VNQEGEEDRFQAHSKLGNRKLLWHGTNMAVVAAILTSGLRIMPHSGGRVGKGIYFASENS
KSAGYVIGMKCGAHHVGYMFLGEVALGREHHINTDNPSLKSPPPGFDSVIARGHTEPDPT
QDTELELDGQQVVVPQGQPVPCPEFSSSTFSQSEYLIYQESQCRLRYLLEVHL

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Family ARTD/PARP family
Function
Mono-ADP-ribosyltransferase that mediates mono-ADP- ribosylation of target proteins and plays a key role in the response to DNA damage. Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins. In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation. Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA. Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ. Suppresses G-quadruplex (G4) structures in response to DNA damage. Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks. Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin. In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP- ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks.

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HGNC ID
HGNC:273
KEGG ID hsa:10039
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PARP3 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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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 PARP3 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 PARP3 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 PARP3 (PARP3) 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.

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Response regulation Mechanistically, pharmacological inhibition or genetic deletion of PARP3 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 PARP3 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.