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Molecule Details

General Information of the Molecule
Name
Proliferating cell nuclear antigen (PCNA)
Synonyms
Cyclin
Gene Name
PCNA
Gene ID
5111
Sequence
MFEARLVQGSILKKVLEALKDLINEACWDISSSGVNLQSMDSSHVSLVQLTLRSEGFDTY
RCDRNLAMGVNLTSMSKILKCAGNEDIITLRAEDNADTLALVFEAPNQEKVSDYEMKLMD
LDVEQLGIPEQEYSCVVKMPSGEFARICRDLSHIGDAVVISCAKDGVKFSASGELGNGNI
KLSQTSNVDKEEEAVTIEMNEPVQLTFALRYLNFFTKATPLSSTVTLSMSADVPLVVEYK
IADMGHLKYYLAPKIEDEEGS
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Function
Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.
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Uniprot ID
PCNA_HUMAN
Pfam
PF02747 ; PF00705
KEGG ID
hsa5111
TTD ID
T21782
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 Fisetin   NP Info  + Cabazitaxel   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Thymoquinone   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Cyclophosphamide   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Esculetin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Canstatin   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Oxaliplatin   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Paclitaxel   NP Info  + Decitabine   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Cucurbitacin D  NP Info  Investigative Cucurbitaceae
References
Reference 1 Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells. Mol Cancer Ther. 2016 Dec;15(12):2863-2874.
Reference 2 Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007 Apr 15;67(8):3853-61.
Reference 3 Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo. J Exp Clin Cancer Res. 2010 Jul 1;29(1):87.
Reference 4 Antiangiogenic effect of low-dose cyclophosphamide combined with ginsenoside Rg3 on Lewis lung carcinoma. Biochem Biophys Res Commun. 2006 Apr 14;342(3):824-8.
Reference 5 Esculetin enhances the inhibitory effect of 5-Fluorouracil on the proliferation, migration and epithelial-mesenchymal transition of colorectal cancer. Cancer Biomark. 2019;24(2):231-240.
Reference 6 Combination of canstatin and arsenic trioxide suppresses the development of hepatocellular carcinoma. Drug Dev Res. 2021 May;82(3):430-439.
Reference 7 Ginsenoside Rg3 Combined with Oxaliplatin Inhibits the Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma Cells via Downregulating PCNA and Cyclin D1. Biol Pharm Bull. 2019 Jun 1;42(6):900-905.
Reference 8 Betulinic acid enhanced the chemical sensitivity of esophageal cancer cells to cisplatin by inducing cell pyroptosis and reducing cell stemness. Ann Palliat Med. 2020 Jul;9(4):1912-1920.
Reference 9 VHL-TGFBI signaling is involved in the synergy between 5-aza-2'-deoxycytidine and paclitaxel against human renal cell carcinoma. J BUON. Mar-Apr 2017;22(2):500-507.
Reference 10 Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer. Cancers (Basel). 2019 Mar 14;11(3):364.
Cite NPCDR
Visitor Map
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