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 T45299 Target Info
Target Name Tissue-type plasminogen activator (PLAT)
Synonyms TPA; T-plasminogen activator; T-PA; Reteplase; Alteplase
Target Type Successful Target
Gene Name PLAT
Biochemical Class Peptidase
UniProt ID
TPA_HUMAN
The Transcription Factors (TFs) Regulating This Target  Top
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 Previous studies in transfected HeLa cells identified two cis-acting regulatory elements within the PLAT promoter responsible for both constitutive and PMA-inducible expression. One of the elements was investigated in a supershift assay using specific antibodies against members of the fos/jun and CREB/ATF families. [1]
Evidence Score (E-score) 2 +
1 Electrophoretic Mobility Shift Assay [2]
2 Nuclear Run-On Transcription Assay, Protein-DNA Binding Assay, Electrophoretic Mobility Shift Assay [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 [3]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [4]
Growth factors [+] 1 Growth factors Co-regulated By This TF +
1 Transforming growth factor beta 2 (TGFB2) Clinical trial Target Target Info [5]
Peptidases [+] 2 Peptidases Co-regulated By This TF +
1 Tissue-type plasminogen activator (PLAT) Successful Target Target Info [1]
2 Urokinase-type plasminogen activator (PLAU) Successful Target Target Info [6]
TF Name cAMP-responsive element-binding (CREB) homodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Regulation Mechanism Previous studies in transfected HeLa cells identified two cis-acting regulatory elements within the PLAT promoter responsible for both constitutive and PMA-inducible expression. One of the elements was investigated in a supershift assay using specific antibodies against members of the fos/jun and CREB/ATF families. [1]
Evidence Score (E-score) 1 +
1 Nuclear Run-On Transcription Assay, Protein-DNA Binding Assay, Electrophoretic Mobility Shift Assay [1]
UniProt ID
CREB1_HUMAN
Sequence
MTMESGAENQQSGDAAVTEAENQQMTVQAQPQIATLAQVSMPAAHATSSAPTVTLVQLPN
GQTVQVHGVIQAAQPSVIQSPQVQTVQSSCKDLKRLFSGTQISTIAESEDSQESVDSVTD
SQKRREILSRRPSYRKILNDLSSDAPGVPRIEEEKSEEETSAPAITTVTVPTPIYQTSSG
QYIAITQGGAIQLANNGTDGVQGLQTLTMTNAAATQPGTTILQYAQTTDGQQILVPSNQV
VVQAASGDVQTYQIRTAPTSTIAPGVVMASSPALPTQPAEEAARKREVRLMKNREAAREC
RRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD
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 [3]
Cytokines / Cytokine receptors [+] 3 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [4]
2 Interleukin 5 receptor alpha (IL5RA) Successful Target Target Info [7]
3 Interleukin-1 beta (IL1B) Successful Target Target Info [8]
Fibronectin proteins [+] 1 Fibronectin proteins Co-regulated By This TF +
1 Fibronectin (FN1) Clinical trial Target Target Info [9]
G protein-coupled receptors [+] 1 G protein-coupled receptors Co-regulated By This TF +
1 Gonadotropin-releasing hormone receptor (GNRHR) Successful Target Target Info [10]
Glucagons [+] 1 Glucagons Co-regulated By This TF +
1 Vasoactive intestinal polypeptide (VIP) Literature-reported Target Target Info [11]
Hormones [+] 2 Hormones Co-regulated By This TF +
1 Erythropoietin (EPO) Clinical trial Target Target Info [12]
2 Parathyroid hormone (PTH) Successful Target Target Info [13]
Immunoglobulins [+] 1 Immunoglobulins Co-regulated By This TF +
1 T-cell surface glycoprotein CD4 (CD4) Successful Target Target Info [14]
Lipoprotein receptors [+] 1 Lipoprotein receptors Co-regulated By This TF +
1 Low-density lipoprotein receptor (LDL-R) Successful Target Target Info [15]
Oxidoreductases [+] 2 Oxidoreductases Co-regulated By This TF +
1 Cholesterol desmolase (CYP11A1) Successful Target Target Info [16]
2 Dopamine beta hydroxylase (DBH) Clinical trial Target Target Info [17]
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Tissue-type plasminogen activator (PLAT) Successful Target Target Info [1]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Early growth response protein 1 (EGR-1) Clinical trial Target Target Info [18]
Transferrins [+] 1 Transferrins Co-regulated By This TF +
1 Transferrin (TF) Clinical trial Target Target Info [19]
References  Top
REF 1 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.
REF 2 Transcription factor E2F is required for efficient expression of the hamster dihydrofolate reductase gene in vitro and in vivo. Mol Cell Biol. 1989 Nov;9(11):4994-5002.
REF 3 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 4 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 5 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 6 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 7 An AP-1 site in the promoter of the human IL-5R alpha gene is necessary for promoter activity in eosinophilic HL60 cells. FEBS Lett. 1998 Sep 4;434(3):251-4.
REF 8 Transcription factors NF-IL6 and CREB recognize a common essential site in the human prointerleukin 1 beta gene. Mol Cell Biol. 1994 Nov;14(11):7285-97.
REF 9 Cyclic AMP inhibits fibronectin gene expression in a newly developed granulosa cell line by a mechanism that suppresses cAMP-responsive element-dependent transcriptional activation. J Biol Chem. 1990 Oct 25;265(30):18219-26.
REF 10 Functional mapping of a placenta-specific upstream promoter for human gonadotropin-releasing hormone receptor gene. Endocrinology. 2001 Apr;142(4):1506-16.
REF 11 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 12 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 13 A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium. J Biol Chem. 1994 Nov 11;269(45):27855-62.
REF 14 CD4 promoter transactivation by human herpesvirus 6. J Virol. 1998 Nov;72(11):8797-805.
REF 15 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 16 Regulatory mechanisms of cAMP-dependent and cell-specific expression of human steroidogenic cytochrome P450scc (CYP11A1) gene. Eur J Biochem. 1994 Jun 15;222(3):825-34.
REF 17 Noradrenergic-specific transcription of the dopamine beta-hydroxylase gene requires synergy of multiple cis-acting elements including at least two Phox2a-binding sites. J Neurosci. 1998 Oct 15;18(20):8247-60.
REF 18 Granulocyte-macrophage colony-stimulating factor and interleukin-3 signaling pathways converge on the CREB-binding site in the human egr-1 promoter. Mol Cell Biol. 1994 Sep;14(9):5975-85.
REF 19 Brain-specific expression of the human transferrin gene. Similar elements govern transcription in oligodendrocytes and in a neuronal cell line. J Biol Chem. 1994 Sep 30;269(39):24504-10.

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