Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10318)
Regulator Name Protein arginine N-methyltransferase 1 (PRMT1)
Synonyms
Histone-arginine N-methyltransferase PRMT1; Interferon receptor 1-bound protein 4
    Click to Show/Hide
Gene Name PRMT1
Gene ID 3276
Regulator Type Protein coding
Uniprot ID Q99873
Sequence
MAAAEAANCIMENFVATLANGMSLQPPLEEVSCGQAESSEKPNAEDMTSKDYYFDSYAHF
GIHEEMLKDEVRTLTYRNSMFHNRHLFKDKVVLDVGSGTGILCMFAAKAGARKVIGIECS
SISDYAVKIVKANKLDHVVTIIKGKVEEVELPVEKVDIIISEWMGYCLFYESMLNTVLYA
RDKWLAPDGLIFPDRATLYVTAIEDRQYKDYKIHWWENVYGFDMSCIKDVAIKEPLVDVV
DPKQLVTNACLIKEVDIYTVKVEDLTFTSPFCLQVKRNDYVHALVAYFNIEFTRCHKRTG
FSTSPESPYTHWKQTVFYMEDYLTVKTGEEIFGTIGMRPNAKNNRDLDFTIDLDFKGQLC
ELSCSTDYRMR

    Click to Show/Hide
Family Protein arginine N-methyltransferase family
Function
Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, FMR1, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4, SERBP1, RBM15, FOXO1, CHTOP and MAP3K5/ASK1. Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway. Methylates RBM15, promoting ubiquitination and degradation of RBM15. Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity. Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity. Methylates MAP3K5/ASK1 at 'Arg-78' and 'Arg-80' which promotes association of MAP3K5 with thioredoxin and negatively regulates MAP3K5 association with TRAF2, inhibiting MAP3K5 stimulation and MAP3K5-induced activation of JNK. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. Plays a role in regulating alternative splicing in the heart.

    Click to Show/Hide
HGNC ID
HGNC:5187
KEGG ID hsa:3276
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PRMT1 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
Browse Drug
Long-chain-fatty-acid--CoA ligase 1 (ACSL1) [Driver]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Responsed Drug GSK3368715 Phase 1
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
HEL cells Erythroleukemia Homo sapiens CVCL_0001
MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
5 x 106 NB4 cells were subcutaneously injected into the flank of 6-7-week-old female nude mice. The tumor number, body weight, and tumor volume were measured every other day. Tumor volumes were estimated using the following formula: tumor volume = (length x width2)/2. When tumor volumes reached 100-200 mm3, the mice were randomly divided into solvent control, RSL3, GSK3368715, or RSL3 + GSK3368715 combination groups (six mice per group). Specifically, for the RSL3 group, mice received intraperitoneal injections of RSL3 at 50 mg/kg 2 days apart. In the GSK3368715 group, GSK3368715 was intraperitoneally injected into mice at a dose of 75 mg/kg for 2 consecutive days per week. For the group that received RSL3 + GSK3368715 combination treatment, GSK3368715 (75 mg/kg) was administered by intraperitoneal injection for the first 2 days. Immediately thereafter, the mice received an intraperitoneal injection of RSL3 (50 mg/kg) 2 days apart. After 1 day of rest, the cycle was repeated until the end of the study on Day 21. Tumor volumes and body weights of the mice were measured and recorded every other day.

    Click to Show/Hide
Response regulation Both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of Acute myeloid leukemia (AML) cells following GSK3368715 treatment. Overall, PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia.
Acute myeloid leukaemia [ICD-11: 2A60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Protein arginine N-methyltransferase 1 (PRMT1) Protein coding
 Regulator Info 
Responsed Drug GSK3368715 Phase 1
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
HEL cells Erythroleukemia Homo sapiens CVCL_0001
MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
5 x 106 NB4 cells were subcutaneously injected into the flank of 6-7-week-old female nude mice. The tumor number, body weight, and tumor volume were measured every other day. Tumor volumes were estimated using the following formula: tumor volume = (length x width2)/2. When tumor volumes reached 100-200 mm3, the mice were randomly divided into solvent control, RSL3, GSK3368715, or RSL3 + GSK3368715 combination groups (six mice per group). Specifically, for the RSL3 group, mice received intraperitoneal injections of RSL3 at 50 mg/kg 2 days apart. In the GSK3368715 group, GSK3368715 was intraperitoneally injected into mice at a dose of 75 mg/kg for 2 consecutive days per week. For the group that received RSL3 + GSK3368715 combination treatment, GSK3368715 (75 mg/kg) was administered by intraperitoneal injection for the first 2 days. Immediately thereafter, the mice received an intraperitoneal injection of RSL3 (50 mg/kg) 2 days apart. After 1 day of rest, the cycle was repeated until the end of the study on Day 21. Tumor volumes and body weights of the mice were measured and recorded every other day.

    Click to Show/Hide
Response regulation Both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of Acute myeloid leukemia (AML) cells following GSK3368715 treatment. Overall, PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia.
GSK3368715 [Phase 1]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Long-chain-fatty-acid--CoA ligase 1 (ACSL1) Driver
 Target Info 
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 NB4 cells Acute promyelocytic leukemia Homo sapiens CVCL_0005
HEL cells Erythroleukemia Homo sapiens CVCL_0001
MOLM-13 cells Adult acute myeloid leukemia Homo sapiens CVCL_2119
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
5 x 106 NB4 cells were subcutaneously injected into the flank of 6-7-week-old female nude mice. The tumor number, body weight, and tumor volume were measured every other day. Tumor volumes were estimated using the following formula: tumor volume = (length x width2)/2. When tumor volumes reached 100-200 mm3, the mice were randomly divided into solvent control, RSL3, GSK3368715, or RSL3 + GSK3368715 combination groups (six mice per group). Specifically, for the RSL3 group, mice received intraperitoneal injections of RSL3 at 50 mg/kg 2 days apart. In the GSK3368715 group, GSK3368715 was intraperitoneally injected into mice at a dose of 75 mg/kg for 2 consecutive days per week. For the group that received RSL3 + GSK3368715 combination treatment, GSK3368715 (75 mg/kg) was administered by intraperitoneal injection for the first 2 days. Immediately thereafter, the mice received an intraperitoneal injection of RSL3 (50 mg/kg) 2 days apart. After 1 day of rest, the cycle was repeated until the end of the study on Day 21. Tumor volumes and body weights of the mice were measured and recorded every other day.

    Click to Show/Hide
Response regulation Both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of Acute myeloid leukemia (AML) cells following GSK3368715 treatment. Overall, PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia.
References
Ref 1 PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. Mol Carcinog. 2023 Aug;62(8):1119-1135. doi: 10.1002/mc.23550. Epub 2023 May 5.