Target Regulator(s) Information (Transcription Factor)

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Target General Information
The Transcription Factors (TFs) Regulating This Target
References
Target General Information  Top
Target ID T21782 Target Info
Target Name Proliferating cell nuclear antigen (PCNA)
Synonyms Cyclin
Target Type Clinical trial Target
Gene Name PCNA
UniProt ID
PCNA_HUMAN
The Transcription Factors (TFs) Regulating This Target  Top
TF Name Tumor suppressor p53 (TP53) homotetramer
Classification Superclass beta-Scaffold Factors with Minor Groove Contacts
Class p53
Family p53
Regulation Type Increase
Regulation Mechanism At low levels, wild-type TP53 transactivates the human PCNA promoter. [1]
Evidence Score (E-score) 2 +
1 Chloramphenicol Acetyltransferase Assay, DNase I Footprint Analysis, Electrophoretic Mobility Shift Assay [1]
2 Electrophoretic Mobility Shift Assay [4]
UniProt ID
P53_HUMAN
Sequence
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK
SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE
RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS
SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP
PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG
GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Acyltransferases [+] 1 Acyltransferases Co-regulated By This TF +
1 Ubiquitin-protein ligase E3 Mdm2 (MDM2) Clinical trial Target Target Info [5]
Apoptosis regulators [+] 1 Apoptosis regulators Co-regulated By This TF +
1 Apoptosis regulator Bcl-2 (BCL-2) Successful Target Target Info [6]
Caveolin proteins [+] 1 Caveolin proteins Co-regulated By This TF +
1 Caveolin 1 (CAV1) Literature-reported Target Target Info [7]
Cyclins [+] 1 Cyclins Co-regulated By This TF +
1 Proliferating cell nuclear antigen (PCNA) Clinical trial Target Target Info [1]
Ester hydrolases [+] 2 Ester hydrolases Co-regulated By This TF +
1 M-phase inducer phosphatase 3 (MPIP3) Literature-reported Target Target Info [8]
2 Phosphatase and tensin homolog (PTEN) Literature-reported Target Target Info [9]
Growth factor binding [+] 1 Growth factor binding Co-regulated By This TF +
1 Insulin-like growth factor-binding protein 3 (IGFBP3) Clinical trial Target Target Info [10]
Methyltransferases [+] 1 Methyltransferases Co-regulated By This TF +
1 DNA [cytosine-5]-methyltransferase 1 (DNMT1) Clinical trial Target Target Info [11]
Peptidases [+] 2 Peptidases Co-regulated By This TF +
1 Caspase-6 (CASP6) Patented-recorded Target Target Info [12]
2 Matrix metalloproteinase-2 (MMP-2) Successful Target Target Info [13]
Small GTPases [+] 1 Small GTPases Co-regulated By This TF +
1 GTPase HRas (HRAS) Literature-reported Target Target Info [14]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Cyclic-AMP-dependent transcription factor ATF-3 (ATF3) Literature-reported Target Target Info [15]
TF Name cAMP-dependent transcription factor 1 (ATF-1) homodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family CREB
Regulation Type Increase
Regulation Mechanism PCNA cellular transcription factors associate with the PERE. In electrophoretic mobility shift assays, the PERE formed P2 and P3 complexes with proteins in nuclear extracts from HeLa or 293 cells. Formation of complexes P2 and P3, which correlates with PCNA promoter activity in vivo, requires the activating transcription factor (ATF) binding site found within the PERE. [2]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [2]
UniProt ID
ATF1_HUMAN
Sequence
MEDSHKSTTSETAPQPGSAVQGAHISHIAQQVSSLSESEESQDSSDSIGSSQKAHGILAR
RPSYRKILKDLSSEDTRGRKGDGENSGVSAAVTSMSVPTPIYQTSSGQYIAIAPNGALQL
ASPGTDGVQGLQTLTMTNSGSTQQGTTILQYAQTSDGQQILVPSNQVVVQTASGDMQTYQ
IRTTPSATSLPQTVVMTSPVTLTSQTTKTDDPQLKREIRLMKNREAARECRRKKKEYVKC
LENRVAVLENQNKTLIEELKTLKDLYSNKSV
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cyclins [+] 2 Cyclins Co-regulated By This TF +
1 Cyclin A2 (CCNA2) Literature-reported Target Target Info [16]
2 Proliferating cell nuclear antigen (PCNA) Clinical trial Target Target Info [2]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [17]
Growth factors [+] 1 Growth factors Co-regulated By This TF +
1 Transforming growth factor beta 2 (TGFB2) Clinical trial Target Target Info [18]
Hormones [+] 1 Hormones Co-regulated By This TF +
1 Erythropoietin (EPO) Clinical trial Target Target Info [19]
Lipoprotein receptors [+] 1 Lipoprotein receptors Co-regulated By This TF +
1 Low-density lipoprotein receptor (LDL-R) Successful Target Target Info [20]
TF Name Delta transcription factor (YY-1) homodimer
Classification Superclass Zinc-coordinating DNA-binding domains
Class Cys2His2 zinc finger domain
Family Ubiquitous factors
Regulation Mechanism The transcription factor YY-1 associates with the initiator element of the PCNA promoter. [2]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [2]
UniProt ID
TYY1_HUMAN
Sequence
MASGDTLYIATDGSEMPAEIVELHEIEVETIPVETIETTVVGEEEEEDDDDEDGGGGDHG
GGGGHGHAGHHHHHHHHHHHPPMIALQPLVTDDPTQVHHHQEVILVQTREEVVGGDDSDG
LRAEDGFEDQILIPVPAPAGGDDDYIEQTLVTVAAAGKSGGGGSSSSGGGRVKKGGGKKS
GKKSYLSGGAGAAGGGGADPGNKKWEQKQVQIKTLEGEFSVTMWSSDEKKDIDHETVVEE
QIIGENSPPDYSEYMTGKKLPPGGIPGIDLSDPKQLAEFARMKPRKIKEDDAPRTIACPH
KGCTKMFRDNSAMRKHLHTHGPRVHVCAECGKAFVESSKLKRHQLVHTGEKPFQCTFEGC
GKRFSLDFNLRTHVRIHTGDRPYVCPFDGCNKKFAQSTNLKSHILTHAKAKNNQ
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cyclins [+] 1 Cyclins Co-regulated By This TF +
1 Proliferating cell nuclear antigen (PCNA) Clinical trial Target Target Info [2]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [21]
Ester hydrolases [+] 1 Ester hydrolases Co-regulated By This TF +
1 M-phase inducer phosphatase 3 (MPIP3) Literature-reported Target Target Info [22]
Glycoproteins [+] 1 Glycoproteins Co-regulated By This TF +
1 Cholesteryl ester transfer protein (CETP) Clinical trial Target Target Info [23]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Dopamine beta hydroxylase (DBH) Clinical trial Target Target Info [24]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Cellular tumor antigen p53 (TP53) Clinical trial Target Target Info [25]
Transferrins [+] 1 Transferrins Co-regulated By This TF +
1 Transferrin (TF) Clinical trial Target Target Info [26]
TF Name E2F transcription factor 4 (E2F-4) homodimer
Classification Superclass Helix-turn-helix
Class Fork head / winged helix
Family Cell-cycle controlling factors
Regulation Mechanism The E2F site, a potential candidate for the cell cycle regulation of the PCNA gene, is located in an approximately 200-bp-long sequence within intron 1, which has all the characteristics of a functional promoter. [3]
Evidence Score (E-score) 1 +
1 DNase I Footprint Analysis, Electrophoretic Mobility Shift Assay [3]
UniProt ID
E2F4_HUMAN
Sequence
MAEAGPQAPPPPGTPSRHEKSLGLLTTKFVSLLQEAKDGVLDLKLAADTLAVRQKRRIYD
ITNVLEGIGLIEKKSKNSIQWKGVGPGCNTREIADKLIELKAEIEELQQREQELDQHKVW
VQQSIRNVTEDVQNSCLAYVTHEDICRCFAGDTLLAIRAPSGTSLEVPIPEGLNGQKKYQ
IHLKSVSGPIEVLLVNKEAWSSPPVAVPVPPPEDLLQSPSAVSTPPPLPKPALAQSQEAS
RPNSPQLTPTAVPGSAEVQGMAGPAAEITVSGGPGTDSKDSGELSSLPLGPTTLDTRPLQ
SSALLDSSSSSSSSSSSSSNSNSSSSSGPNPSTSFEPIKADPTGVLELPKELSEIFDPTR
ECMSSELLEELMSSEVFAPLLRLSPPPGDHDYIYNLDESEGVCDLFDVPVLNL
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cyclins [+] 1 Cyclins Co-regulated By This TF +
1 Proliferating cell nuclear antigen (PCNA) Clinical trial Target Target Info [3]
TF Name Regulatory factor X 1 (RFX1) homodimer
Classification Superclass Helix-turn-helix
Class Fork head / winged helix
Regulation Mechanism PCNA cellular transcription factors associate with the PERE. In electrophoretic mobility shift assays, the PERE formed P1 complexes with proteins in nuclear extracts from HeLa or 293 cells. The hepatitis B virus enhancer-associated protein RFX1 constitutes a major component of the P1 complex. [2]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [2]
UniProt ID
RFX1_HUMAN
Sequence
MATQAYTELQAAPPPSQPPQAPPQAQPQPPPPPPPAAPQPPQPPTAAATPQPQYVTELQS
PQPQAQPPGGQKQYVTELPAVPAPSQPTGAPTPSPAPQQYIVVTVSEGAMRASETVSEAS
PGSTASQTGVPTQVVQQVQGTQQRLLVQTSVQAKPGHVSPLQLTNIQVPQQALPTQRLVV
QSAAPGSKGGQVSLTVHGTQQVHSPPEQSPVQANSSSSKTAGAPTGTVPQQLQVHGVQQS
VPVTQERSVVQATPQAPKPGPVQPLTVQGLQPVHVAQEVQQLQQVPVPHVYSSQVQYVEG
GDASYTASAIRSSTYSYPETPLYTQTASTSYYEAAGTATQVSTPATSQAVASSGSMPMYV
SGSQVVASSTSTGAGASNSSGGGGSGGGGGGGGGGGGGGSGSTGGGGSGAGTYVIQGGYM
LGSASQSYSHTTRASPATVQWLLDNYETAEGVSLPRSTLYCHYLLHCQEQKLEPVNAASF
GKLIRSVFMGLRTRRLGTRGNSKYHYYGLRIKASSPLLRLMEDQQHMAMRGQPFSQKQRL
KPIQKMEGMTNGVAVGQQPSTGLSDISAQVQQYQQFLDASRSLPDFTELDLQGKVLPEGV
GPGDIKAFQVLYREHCEAIVDVMVNLQFTLVETLWKTFWRYNLSQPSEAPPLAVHDEAEK
RLPKAILVLLSKFEPVLQWTKHCDNVLYQGLVEILIPDVLRPIPSALTQAIRNFAKSLES
WLTHAMVNIPEEMLRVKVAAAGAFAQTLRRYTSLNHLAQAARAVLQNTAQINQMLSDLNR
VDFANVQEQASWVCRCEDRVVQRLEQDFKVTLQQQNSLEQWAAWLDGVVSQVLKPYQGSA
GFPKAAKLFLLKWSFYSSMVIRDLTLRSAASFGSFHLIRLLYDEYMYYLIEHRVAQAKGE
TPIAVMGEFANLATSLNPLDPDKDEEEEEEEESEDELPQDISLAAGGESPALGPETLEPP
AKLARTDARGLFVQALPSS
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cyclins [+] 1 Cyclins Co-regulated By This TF +
1 Proliferating cell nuclear antigen (PCNA) Clinical trial Target Target Info [2]
References  Top
REF 1 Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter. Mol Cell Biol. 1995 Dec;15(12):6785-93.
REF 2 Transcription factors RFX1/EF-C and ATF-1 associate with the adenovirus E1A-responsive element of the human proliferating cell nuclear antigen promoter. Nucleic Acids Res. 1995 Sep 25;23(18):3732-41.
REF 3 In vivo structure of two divergent promoters at the human PCNA locus. Synthesis of antisense RNA and S phase-dependent binding of E2F complexes in intron 1. J Biol Chem. 1999 Sep 24;274(39):27829-38.
REF 4 Transcriptional activation of the human proliferating-cell nuclear antigen promoter by p53. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):895-9.
REF 5 A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res. 1995 Jul 25;23(14):2584-92.
REF 6 Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene. 2001 Jan 11;20(2):240-51.
REF 7 p53 regulates caveolin gene transcription, cell cholesterol, and growth by a novel mechanism. Biochemistry. 2000 Feb 29;39(8):1966-72.
REF 8 Identification of a novel class of genomic DNA-binding sites suggests a mechanism for selectivity in target gene activation by the tumor suppressor protein p53. Genes Dev. 1998 Jul 15;12(14):2102-7.
REF 9 Regulation of PTEN transcription by p53. Mol Cell. 2001 Aug;8(2):317-25.
REF 10 Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature. 1995 Oct 19;377(6550):646-9.
REF 11 p53-mediated repression of DNA methyltransferase 1 expression by specific DNA binding. Cancer Res. 2003 Oct 15;63(20):6579-82.
REF 12 Apoptotic threshold is lowered by p53 transactivation of caspase-6. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9492-7.
REF 13 Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. Mol Cell Biol. 1997 Nov;17(11):6330-8.
REF 14 Transcriptional regulation of the c-H-ras1 gene by the P53 protein is implicated in the development of human endometrial and ovarian tumours. Oncogene. 1998 Jun 11;16(23):3013-7.
REF 15 Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53. Biochem Biophys Res Commun. 2002 Oct 11;297(5):1302-10.
REF 16 Down-regulation of the cyclin A promoter in differentiating human embryonal carcinoma cells is mediated by depletion of ATF-1 and ATF-2 in the complex at the ATF/CRE site. Exp Cell Res. 1995 Feb;216(2):422-30.
REF 17 The proximal regulatory element of the interferon-gamma promoter mediates selective expression in T cells. J Biol Chem. 1996 Dec 13;271(50):31964-72.
REF 18 Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2. Nature. 1992 Jul 23;358(6384):331-4.
REF 19 The transcription factors ATF-1 and CREB-1 bind constitutively to the hypoxia-inducible factor-1 (HIF-1) DNA recognition site. Nucleic Acids Res. 1995 Nov 25;23(22):4542-50.
REF 20 Identification of a novel sterol-independent regulatory element in the human low density lipoprotein receptor promoter. J Biol Chem. 2000 Feb 18;275(7):5214-21.
REF 21 The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: inhibition of AP1 binding and activation of a silence... Mol Cell Biol. 1996 Sep;16(9):4744-53.
REF 22 Characterization of the TATA-less core promoter of the cell cycle-regulated cdc25C gene. Nucleic Acids Res. 1997 Dec 15;25(24):4933-9.
REF 23 Sterol regulatory element binding protein-1 activates the cholesteryl ester transfer protein gene in vivo but is not required for sterol up-regulation of gene expression. J Biol Chem. 1998 Aug 28;273(35):22409-14.
REF 24 Multiple protein factors interact with the cis-regulatory elements of the proximal promoter in a cell-specific manner and regulate transcription of the dopamine beta-hydroxylase gene. J Neurosci. 1996 Jul 1;16(13):4102-12.
REF 25 YY1 and NF1 both activate the human p53 promoter by alternatively binding to a composite element, and YY1 and E1A cooperate to amplify p53 promoter activity. Mol Cell Biol. 1996 Oct;16(10):5933-45.
REF 26 YY1 and Sp1 transcription factors bind the human transferrin gene in an age-related manner. J Gerontol A Biol Sci Med Sci. 1996 Jan;51(1):B66-75.

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