Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10077)
Regulator Name Retinoblastoma-associated protein (RB1)
Synonyms
p105-Rb; p110-RB1; pRb; pp110
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Gene Name RB1
Gene ID 5925
Regulator Type Protein coding
Uniprot ID P06400
Sequence
MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPLVRLEFEETEEPDFTAL
CQKLKIPDHVRERAWLTWEKVSSVDGVLGGYIQKKKELWGICIFIAAVDLDEMSFTFTEL
QKNIEISVHKFFNLLKEIDTSTKVDNAMSRLLKKYDVLFALFSKLERTCELIYLTQPSSS
ISTEINSALVLKVSWITFLLAKGEVLQMEDDLVISFQLMLCVLDYFIKLSPPMLLKEPYK
TAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKEHECNIDEVKNVYFKNFIPFM
NSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDARLFLDHDKTLQTDSIDSFETQRTPRKS
NLDEEVNVIPPHTPVRTVMNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVK
DIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDN
IFHMSLLACALEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEG
NLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNH
TAADMYLSPVRSPKKKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYL
RLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLK
FKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLS
PIPHIPRSPYKFPSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFG
TSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQK
LAEMTSTRTRMQKQKMNDSMDTSNKEEK

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Family Retinoblastoma protein (RB) family
Function
Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle. The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes. Both physically blocks E2Fs transactivating domain and recruits chromatin- modifying enzymes that actively repress transcription. Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase. RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1- dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex.

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HGNC ID
HGNC:9884
KEGG ID hsa:5925
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
RB1 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
Long-chain-fatty-acid--CoA ligase 4 (ACSL4) [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 Prostate cancer ICD-11: 2C82
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model
 LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
PC-3 cells Prostate carcinoma Homo sapiens CVCL_0035
22Rv1 cells Prostate carcinoma Homo sapiens CVCL_1045
DU145 cells Prostate carcinoma Homo sapiens CVCL_0105
LNCaP C4-2 cells Prostate carcinoma Homo sapiens CVCL_4782
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
RWPE-1 cells Normal Homo sapiens CVCL_3791
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
1 x 106 shCT or shRB PC-3 cells were mixed with 100 uL Matrigel (Corning) and implanted subcutaneously into the right flanks of 6- to 8-week-old male nude mice. When tumor volumes were approximately 80-100 mm3 in PC3 xenografts or circulating RFP tumor cells had begun to emerge in peripheral blood of PPR-RFP mice (around 7.5 months), vehicle or JKE-1674 (25 mg/kg, dissolved in 10% ethanol and 90% PEG-400, Sigma-Aldrich) were administered orally to mice every other day.

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Response regulation The regulation of ferroptosis by the RB1/E2F/ACSL4 axis and highlight the therapeutic potential of ferroptosis induction in the treatment of RB1 loss driven prostate cancer growth and metastasis and perhaps other RB1-deficient malignancies.
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_6714
In Vivo Model
Six week-old female Balb/cnude mice (Janvier, Le Genest Saint Isle, France) were injected with HCC cells (10 x 106 cells) stably transfected with the vector pGL4.51 [luc2/CMV/neo] (Promega) encoding the luciferase reporter gene luc2 (Photinus pyralis). When the first tumours appeared, mice were randomly assigned into four groups: control or shRb, receiving sorafenib administered by oral gavage (30 mg/kg/d, resuspended in Cremophore EL) or vehicle alone.

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Response regulation Upon exposure to sorafenib, the Rb (RB1)-negative status of hepatocellular carcinoma cells promotes the occurrence of ferroptosis, a form of oxidative necrosis. The findings highlight the role of Rb in the response of HCC cells to sorafenib and the regulation of ferroptosis.
Prostate cancer [ICD-11: 2C82]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Retinoblastoma-associated protein (RB1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model
 LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
PC-3 cells Prostate carcinoma Homo sapiens CVCL_0035
22Rv1 cells Prostate carcinoma Homo sapiens CVCL_1045
DU145 cells Prostate carcinoma Homo sapiens CVCL_0105
LNCaP C4-2 cells Prostate carcinoma Homo sapiens CVCL_4782
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
RWPE-1 cells Normal Homo sapiens CVCL_3791
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
1 x 106 shCT or shRB PC-3 cells were mixed with 100 uL Matrigel (Corning) and implanted subcutaneously into the right flanks of 6- to 8-week-old male nude mice. When tumor volumes were approximately 80-100 mm3 in PC3 xenografts or circulating RFP tumor cells had begun to emerge in peripheral blood of PPR-RFP mice (around 7.5 months), vehicle or JKE-1674 (25 mg/kg, dissolved in 10% ethanol and 90% PEG-400, Sigma-Aldrich) were administered orally to mice every other day.

    Click to Show/Hide
Response regulation The regulation of ferroptosis by the RB1/E2F/ACSL4 axis and highlight the therapeutic potential of ferroptosis induction in the treatment of RB1 loss driven prostate cancer growth and metastasis and perhaps other RB1-deficient malignancies.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Retinoblastoma-associated protein (RB1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
PLC/PRF/5 cells Hepatocellular carcinoma Homo sapiens CVCL_6714
In Vivo Model
Six week-old female Balb/cnude mice (Janvier, Le Genest Saint Isle, France) were injected with HCC cells (10 x 106 cells) stably transfected with the vector pGL4.51 [luc2/CMV/neo] (Promega) encoding the luciferase reporter gene luc2 (Photinus pyralis). When the first tumours appeared, mice were randomly assigned into four groups: control or shRb, receiving sorafenib administered by oral gavage (30 mg/kg/d, resuspended in Cremophore EL) or vehicle alone.

    Click to Show/Hide
Response regulation Upon exposure to sorafenib, the Rb (RB1)-negative status of hepatocellular carcinoma cells promotes the occurrence of ferroptosis, a form of oxidative necrosis. The findings highlight the role of Rb in the response of HCC cells to sorafenib and the regulation of ferroptosis.
References
Ref 1 RB1-deficient prostate tumor growth and metastasis are vulnerable to ferroptosis induction via the E2F/ACSL4 axis. J Clin Invest. 2023 May 15;133(10):e166647. doi: 10.1172/JCI166647.
Ref 2 The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells. Cancer Lett. 2015 Jan 28;356(2 Pt B):971-7. doi: 10.1016/j.canlet.2014.11.014. Epub 2014 Nov 12.