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Molecule Details

General Information of the Molecule
Name
Retinoblastoma-associated protein (RB1)
Synonyms
p105-Rb; p110-RB1; pRb; Rb; pp110
Gene Name
RB1
Gene ID
5925
Sequence
MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPLVRLEFEETEEPDFTAL
CQKLKIPDHVRERAWLTWEKVSSVDGVLGGYIQKKKELWGICIFIAAVDLDEMSFTFTEL
QKNIEISVHKFFNLLKEIDTSTKVDNAMSRLLKKYDVLFALFSKLERTCELIYLTQPSSS
ISTEINSALVLKVSWITFLLAKGEVLQMEDDLVISFQLMLCVLDYFIKLSPPMLLKEPYK
TAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKEHECNIDEVKNVYFKNFIPFM
NSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDARLFLDHDKTLQTDSIDSFETQRTPRKS
NLDEEVNVIPPHTPVRTVMNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVK
DIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDN
IFHMSLLACALEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEG
NLTREMIKHLERCEHRIMESLAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNH
TAADMYLSPVRSPKKKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYL
RLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLK
FKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLS
PIPHIPRSPYKFPSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFG
TSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQK
LAEMTSTRTRMQKQKMNDSMDTSNKEEK
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Function
Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. 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 (By similarity); (Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.
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Uniprot ID
RB_HUMAN
Pfam
PF11934 ; PF01858 ; PF01857 ; PF08934
KEGG ID
hsa5925
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Honokiol   NP Info  + Rosiglitazone   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Nobiletin   NP Info  + Sorafenib   Drug Info 
                    Structure +
          Phosphorylation Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Phosphorylation of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Silibinin   NP Info  + Indole-3-carbinol   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Phosphorylation of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Erlotinib   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Phosphorylation of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Sunitinib   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Phosphorylation of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Flavopiridol   NP Info  + Depsipeptide   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Phosphorylation of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Flavopiridol   NP Info  + Trastuzumab   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Phosphorylation of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Kaempferol   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Phosphorylation of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Gefitinib   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Phosphorylation of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Tangeretin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
References
Reference 1 Combined effect of honokiol and rosiglitazone on cell growth inhibition through enhanced G0/G1 phase arrest in hepatoma cells. J Chin Med Assoc. 2016 Aug;79(8):415-21.
Reference 2 Enhanced inhibition of lung adenocarcinoma by combinatorial treatment with indole-3-carbinol and silibinin in A/J mice. Carcinogenesis. 2011 Apr;32(4):561-7.
Reference 3 Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
Reference 4 Curcumin potentiates the ability of sunitinib to eliminate the VHL-lacking renal cancer cells 786-O: rapid inhibition of Rb phosphorylation as a preamble to cyclin D1 inhibition. Anticancer Agents Med Chem. 2013 Dec;13(10):1508-13.
Reference 5 Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: activation of the mitochondria-dependent death-signaling pathway. J Thorac Cardiovasc Surg. 2003 May;125(5):1132-42.
Reference 6 Flavopiridol and trastuzumab synergistically inhibit proliferation of breast cancer cells: association with selective cooperative inhibition of cyclin D1-dependent kinase and Akt signaling pathways. Mol Cancer Ther. 2002 Jul;1(9):695-706.
Reference 7 Kaempferol enhances cisplatin's effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cMyc. Cancer Cell Int. 2010 May 11;10:16.
Reference 8 Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells. Nutr Cancer. 2019;71(8):1299-1312.
Reference 9 Synergistic therapy with tangeretin and 5-fluorouracil accelerates the ROS/JNK mediated apoptotic pathway in human colorectal cancer cell. Food Chem Toxicol. 2020 Sep;143:111529.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China