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 T17758 Target Info
Target Name Urokinase-type plasminogen activator (PLAU)
Synonyms UPA; U-plasminogen activator
Target Type Successful Target
Gene Name PLAU
Biochemical Class Peptidase
UniProt ID
UROK_HUMAN
The Transcription Factors (TFs) Regulating This Target  Top
TF Name c-Jun/c-Fos (AP-1) heterodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family AP-1(-like) components
Regulation Mechanism The uPA (also referred as PLAU) enhancer regulation involves the increased expression and phosphorylation of multiple AP-1 components such as c-Jun, JunD, and ATF-2, along with the IL-1- and TPA-dependent activation of the ets family member Ets-2. [1]
Evidence Score (E-score) 3 +
1 DNase I Footprint Analysis [1]
2 DNase I Footprint Analysis [3]
3 Reporter Assay [4]
UniProt ID
JUN_HUMAN/FOS_HUMAN
Sequence
MTAKMETTFYDDALNASFLPSESGPYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL
LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE
LHSQNTLPSVTSAAQPVNGAGMVAPAVASVAGGSGSGGFSASLHSEPPVYANLSNFNPGA
LSSGGGAPSYGAAGLAFPAQPQQQQQPPHHLPQQMPVQHPRLQALKEEPQTVPEMPGETP
PLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELASTANM
LREQVAQLKQKVMNHVNSGCQLMLTQQLQTF
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Acyltransferases [+] 1 Acyltransferases Co-regulated By This TF +
1 Glutathione S-transferase P (GSTP1) Clinical trial Target Target Info [6]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [7]
Endothelins/sarafotoxins [+] 1 Endothelins/sarafotoxins Co-regulated By This TF +
1 Endothelin-1 (EDN1) Literature-reported Target Target Info [8]
G protein-coupled receptors [+] 1 G protein-coupled receptors Co-regulated By This TF +
1 Gonadotropin-releasing hormone receptor (GNRHR) Successful Target Target Info [9]
Glucagons [+] 1 Glucagons Co-regulated By This TF +
1 Vasoactive intestinal polypeptide (VIP) Literature-reported Target Target Info [10]
Hormones [+] 1 Hormones Co-regulated By This TF +
1 Corticoliberin (CRH) Literature-reported Target Target Info [11]
Integrins [+] 1 Integrins Co-regulated By This TF +
1 Integrin alpha-2 (ITGA2) Clinical trial Target Target Info [12]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Quinone reductase 1 (NQO1) Clinical trial Target Target Info [13]
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Urokinase-type plasminogen activator (PLAU) Successful Target Target Info [1]
Somatotropin / Prolactins [+] 1 Somatotropin / Prolactins Co-regulated By This TF +
1 Prolactin (PRL) Discontinued Target Target Info [14]
Transcription factors [+] 2 Transcription factors Co-regulated By This TF +
1 Cellular tumor antigen p53 (TP53) Clinical trial Target Target Info [15]
2 Transcription factor AP-1 (JUN) Discontinued Target Target Info [16]
TF Name JunD proto-oncogene (Jun-D) homodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family AP-1(-like) components
Subfamily Jun
Regulation Mechanism The PLAU enhancer regulation involves the increased expression and phosphorylation of multiple AP-1 components such as c-Jun, Jun-D, and ATF-2, along with the IL-1- and TPA-dependent activation of the ets family member Ets-2. [1]
Evidence Score (E-score) 2 +
1 DNase I Footprint Analysis [1]
2 Electrophoretic Mobility Shift Assay [5]
UniProt ID
JUND_HUMAN
Sequence
METPFYGDEALSGLGGGASGSGGSFASPGRLFPGAPPTAAAGSMMKKDALTLSLSEQVAA
ALKPAAAPPPTPLRADGAPSAAPPDGLLASPDLGLLKLASPELERLIIQSNGLVTTTPTS
SQFLYPKVAASEEQEFAEGFVKALEDLHKQNQLGAGAAAAAAAAAAGGPSGTATGSAPPG
ELAPAAAAPEAPVYANLSSYAGGAGGAGGAATVAFAAEPVPFPPPPPPGALGPPRLAALK
DEPQTVPDVPSFGESPPLSPIDMDTQERIKAERKRLRNRIAASKCRKRKLERISRLEEKV
KTLKSQNTELASTASLLREQVAQLKQKVLSHVNSGCQLLPQHQVPAY
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Urokinase-type plasminogen activator (PLAU) Successful Target Target Info [1]
TF Name cAMP-dependent transcription factor 2 (ATF-2) homodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family AP-1(-like) components
Subfamily CRE-BP/ATF
Regulation Mechanism The uPA (also referred as PLAU) enhancer regulation involves the increased expression and phosphorylation of multiple AP-1 components such as c-Jun, JunD, and ATF-2, along with the IL-1- and TPA-dependent activation of the ets family member Ets-2. [1]
Evidence Score (E-score) 1 +
1 DNase I Footprint Analysis [1]
UniProt ID
ATF2_HUMAN
Sequence
MKFKLHVNSARQYKDLWNMSDDKPFLCTAPGCGQRFTNEDHLAVHKHKHEMTLKFGPARN
DSVIVADQTPTPTRFLKNCEEVGLFNELASPFENEFKKASEDDIKKMPLDLSPLATPIIR
SKIEEPSVVETTHQDSPLPHPESTTSDEKEVPLAQTAQPTSAIVRPASLQVPNVLLTSSD
SSVIIQQAVPSPTSSTVITQAPSSNRPIVPVPGPFPLLLHLPNGQTMPVAIPASITSSNV
HVPAAVPLVRPVTMVPSVPGIPGPSSPQPVQSEAKMRLKAALTQQHPPVTNGDTVKGHGS
GLVRTQSEESRPQSLQQPATSTTETPASPAHTTPQTQSTSGRRRRAANEDPDEKRRKFLE
RNRAAASRCRQKRKVWVQSLEKKAEDLSSLNGQLQSEVTLLRNEVAQLKQLLLAHKDCPV
TAMQKKSGYHTADKDDSSEDISVPSSPHTEAIQHSSVSTSNGVSSTSKAEAVATSVLTQM
ADQSTEPALSQIVMAPSSQSQPSGS
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Apoptosis regulators [+] 1 Apoptosis regulators Co-regulated By This TF +
1 Apoptosis regulator Bcl-2 (BCL-2) Successful Target Target Info [17]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [18]
Growth factors [+] 1 Growth factors Co-regulated By This TF +
1 Transforming growth factor beta 2 (TGFB2) Clinical trial Target Target Info [19]
Peptidases [+] 2 Peptidases Co-regulated By This TF +
1 Tissue-type plasminogen activator (PLAT) Successful Target Target Info [20]
2 Urokinase-type plasminogen activator (PLAU) Successful Target Target Info [1]
TF Name c-Jun/ATF-2 (AP-1) heterodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family AP-1(-like) components
Subfamily Jun
Regulation Mechanism The uPA (also referred as PLAU) enhancer regulation involves the increased expression and phosphorylation of multiple AP-1 components such as c-Jun, JunD, and ATF-2, along with the IL-1- and TPA-dependent activation of the ets family member Ets-2. [1]
Evidence Score (E-score) 1 +
1 DNase I Footprint Analysis [1]
UniProt ID
JUN_HUMAN/ATF2_HUMAN
Sequence
MTAKMETTFYDDALNASFLPSESGPYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL
LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE
LHSQNTLPSVTSAAQPVNGAGMVAPAVASVAGGSGSGGFSASLHSEPPVYANLSNFNPGA
LSSGGGAPSYGAAGLAFPAQPQQQQQPPHHLPQQMPVQHPRLQALKEEPQTVPEMPGETP
PLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELASTANM
LREQVAQLKQKVMNHVNSGCQLMLTQQLQTF
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Urokinase-type plasminogen activator (PLAU) Successful Target Target Info [1]
TF Name Homeobox protein PBX1 (PBX1)
Classification Superclass Helix-turn-helix
Class Homeo domain
Family Homeo domain only
Subfamily PBC
Regulation Mechanism PBX results in a strong DNA binding affinity towards the TGACAG target site of the PLAU promoter. [2]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [2]
UniProt ID
PBX1_HUMAN
Sequence
MDEQPRLMHSHAGVGMAGHPGLSQHLQDGAGGTEGEGGRKQDIGDILQQIMTITDQSLDE
AQARKHALNCHRMKPALFNVLCEIKEKTVLSIRGAQEEEPTDPQLMRLDNMLLAEGVAGP
EKGGGSAAAAAAAAASGGAGSDNSVEHSDYRAKLSQIRQIYHTELEKYEQACNEFTTHVM
NLLREQSRTRPISPKEIERMVSIIHRKFSSIQMQLKQSTCEAVMILRSRFLDARRKRRNF
NKQATEILNEYFYSHLSNPYPSEEAKEELAKKCGITVSQVSNWFGNKRIRYKKNIGKFQE
EANIYAAKTAVTATNVSAHGSQANSPSTPNSAGSSSSFNMSNSGDLFMSVQSLNGDSYQG
AQVGANVQSQVDTLRHVISQTGGYSDGLAASQMYSPQGISANGGWQDATTPSSVTSPTEG
PGSVHSDTSN
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Urokinase-type plasminogen activator (PLAU) Successful Target Target Info [2]
TF Name Homeobox protein PBX2 (PBX2)
Classification Superclass Helix-turn-helix
Class Homeo domain
Family Homeo domain only
Subfamily PBC
Regulation Mechanism PBX results in a strong DNA binding affinity towards the TGACAG target site of the PLAU promoter. [2]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [2]
UniProt ID
PBX2_HUMAN
Sequence
MDERLLGPPPPGGGRGGLGLVSGEPGGPGEPPGGGDPGGGSGGVPGGRGKQDIGDILQQI
MTITDQSLDEAQAKKHALNCHRMKPALFSVLCEIKEKTGLSIRSSQEEEPVDPQLMRLDN
MLLAEGVAGPEKGGGSAAAAAAAAASGGGVSPDNSIEHSDYRSKLAQIRHIYHSELEKYE
QACNEFTTHVMNLLREQSRTRPVAPKEMERMVSIIHRKFSAIQMQLKQSTCEAVMILRSR
FLDARRKRRNFSKQATEVLNEYFYSHLSNPYPSEEAKEELAKKCGITVSQVSNWFGNKRI
RYKKNIGKFQEEANIYAVKTAVSVTQGGHSRTSSPTPPSSAGSGGSFNLSGSGDMFLGMP
GLNGDSYSASQVESLRHSMGPGGYGDNLGGGQMYSPREMRANGSWQEAVTPSSVTSPTEG
PGSVHSDTSN
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Urokinase-type plasminogen activator (PLAU) Successful Target Target Info [2]
References  Top
REF 1 Role of distinct mitogen-activated protein kinase pathways and cooperation between Ets-2, ATF-2, and Jun family members in human urokinase-type plasminogen activator gene induction by interleukin-1 and tetradecanoyl phorbol acetate. Mol Cell Biol. 1999 Sep;19(9):6240-52.
REF 2 Prep1, a novel functional partner of Pbx proteins. EMBO J. 1998 Mar 2;17(5):1423-33.
REF 3 Heterodimerization of c-Jun with ATF-2 and c-Fos is required for positive and negative regulation of the human urokinase enhancer. Oncogene. 1995 Jul 20;11(2):365-76.
REF 4 Urokinase-type plasminogen activator gene regulation by polyomavirus middle-T antigen. Oncogene. 1995 Dec 7;11(11):2383-91.
REF 5 Requirement of an upstream AP-1 motif for the constitutive and phorbol ester-inducible expression of the urokinase-type plasminogen activator recep... J Biol Chem. 1996 Sep 20;271(38):23176-84.
REF 6 Involvement of Jun and Fos proteins in regulating transcriptional activation of the human pi class glutathione S-transferase gene in multidrug-resi... J Biol Chem. 1994 Jun 10;269(23):16397-402.
REF 7 Negative transcriptional regulation of the interferon-gamma promoter by glucocorticoids and dominant negative mutants of c-Jun. J Biol Chem. 1995 May 26;270(21):12548-56.
REF 8 Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP. J Biol Chem. 2001 Apr 20;276(16):12645-53.
REF 9 Functional mapping of a placenta-specific upstream promoter for human gonadotropin-releasing hormone receptor gene. Endocrinology. 2001 Apr;142(4):1506-16.
REF 10 Cyclic AMP- and phorbol ester-induced transcriptional activation are mediated by the same enhancer element in the human vasoactive intestinal peptide gene. J Biol Chem. 1991 Feb 25;266(6):3882-7.
REF 11 Composite glucocorticoid regulation at a functionally defined negative glucocorticoid response element of the human corticotropin-releasing hormone gene. Mol Endocrinol. 1999 Oct;13(10):1629-44.
REF 12 The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene: two tandem AP1 sites and the mitogen-activated protein kinase signal... Blood. 1999 Mar 1;93(5):1600-11.
REF 13 Human antioxidant-response-element-mediated regulation of type 1 NAD(P)H:quinone oxidoreductase gene expression. Effect of sulfhydryl modifying age... Eur J Biochem. 1994 Nov 15;226(1):31-9.
REF 14 Thyroid hormone inhibits the human prolactin gene promoter by interfering with activating protein-1 and estrogen stimulations. Mol Endocrinol. 1997 Jun;11(7):986-96.
REF 15 Expression of human p53 requires synergistic activation of transcription from the p53 promoter by AP-1, NF-kappaB and Myc/Max. Oncogene. 1999 Apr 29;18(17):2728-38.
REF 16 The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875-85.
REF 17 Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. Mol Cell Biol. 1996 Oct;16(10):5546-56.
REF 18 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 19 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 20 Differential binding of cAMP-responsive-element (CRE)-binding protein-1 and activating transcription factor-2 to a CRE-like element in the human tissue-type plasminogen activator (t-PA) gene promoter correlates with opposite regulation of t-PA by phorbol ester in HT-1080 and HeLa cells. Eur J Biochem. 1996 May 1;237(3):532-8.

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