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 T68251 Target Info
Target Name Matrix metalloproteinase-2 (MMP-2)
Synonyms TBE-1; Matrix metalloproteinase 2; CLG4A; 72 kDa type IV collagenase; 72 kDa gelatinase
Target Type Successful Target
Gene Name MMP2
Biochemical Class Peptidase
UniProt ID
MMP2_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 Mechanism The study identified a perfect TP53 binding site in the promoter of the human type IV collagenase (also called 72-kDa gelatinase or matrix metalloproteinase 2 [MMP-2]) gene. [1]
Evidence Score (E-score) 2 +
1 Electrophoretic Mobility Shift Assay [3]
2 Luciferase Reporter Assay, Electrophoretic Mobility Shift Assay [1]
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 [4]
Apoptosis regulators [+] 1 Apoptosis regulators Co-regulated By This TF +
1 Apoptosis regulator Bcl-2 (BCL-2) Successful Target Target Info [5]
Caveolin proteins [+] 1 Caveolin proteins Co-regulated By This TF +
1 Caveolin 1 (CAV1) Literature-reported Target Target Info [6]
Cyclins [+] 1 Cyclins Co-regulated By This TF +
1 Proliferating cell nuclear antigen (PCNA) Clinical trial Target Target Info [7]
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 [1]
Small GTPases [+] 1 Small GTPases Co-regulated By This TF +
1 GTPase HRas (HRAS) Literature-reported Target Target Info [13]
Transcription factors [+] 1 Transcription factors Co-regulated By This TF +
1 Cyclic-AMP-dependent transcription factor ATF-3 (ATF3) Literature-reported Target Target Info [14]
TF Name Activator protein 2 (AP-2) homodimer
Classification Superclass Basic Domains
Class bHSH
Family AP-2
Regulation Mechanism The cell type-specific transcription factor AP-2 is an important transcription factor for the activation of the type IV 72-kDa collagenase (MMP7) promoter and that adenovirus E1A 243-amino acid protein represses this promoter by targeting AP-2. [2]
Evidence Score (E-score) 1 +
1 Chloramphenicol Acetyltransferase Assay, Electrophoretic Mobility Shift Assay [2]
UniProt ID
AP2A_HUMAN
Sequence
MLWKLTDNIKYEDCEDRHDGTSNGTARLPQLGTVGQSPYTSAPPLSHTPNADFQPPYFPP
PYQPIYPQSQDPYSHVNDPYSLNPLHAQPQPQHPGWPGQRQSQESGLLHTHRGLPHQLSG
LDPRRDYRRHEDLLHGPHALSSGLGDLSIHSLPHAIEEVPHVEDPGINIPDQTVIKKGPV
SLSKSNSNAVSAIPINKDNLFGGVVNPNEVFCSVPGRLSLLSSTSKYKVTVAEVQRRLSP
PECLNASLLGGVLRRAKSKNGGRSLREKLDKIGLNLPAGRRKAANVTLLTSLVEGEAVHL
ARDFGYVCETEFPAKAVAEFLNRQHSDPNEQVTRKNMLLATKQICKEFTDLLAQDRSPLG
NSRPNPILEPGIQSCLTHFNLISHGFGSPAVCAAVTALQNYLTEALKAMDKMYLSNNPNS
HTDNNAKSSDKEEKHRK
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 [15]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Interferon-gamma (IFNG) Successful Target Target Info [16]
Ester hydrolases [+] 1 Ester hydrolases Co-regulated By This TF +
1 Acetylcholinesterase (AChE) Successful Target Target Info [17]
Growth factors [+] 1 Growth factors Co-regulated By This TF +
1 Vascular endothelial growth factor A (VEGFA) Successful Target Target Info [18]
Kinases [+] 1 Kinases Co-regulated By This TF +
1 Serine/threonine-protein kinase pim-1 (PIM1) Clinical trial Target Target Info [19]
Oxidoreductases [+] 3 Oxidoreductases Co-regulated By This TF +
1 Dopamine beta hydroxylase (DBH) Clinical trial Target Target Info [20]
2 Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1) Clinical trial Target Target Info [21]
3 Quinone reductase 1 (NQO1) Clinical trial Target Target Info [22]
Peptidases [+] 2 Peptidases Co-regulated By This TF +
1 Matrix metalloproteinase-2 (MMP-2) Successful Target Target Info [2]
2 Neutral endopeptidase (MME) Clinical trial Target Target Info [23]
Pro-neuropeptides [+] 1 Pro-neuropeptides Co-regulated By This TF +
1 Neuropeptide Y (NPY) Literature-reported Target Target Info [24]
References  Top
REF 1 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 2 Repression of a matrix metalloprotease gene by E1A correlates with its ability to bind to cell type-specific transcription factor AP-2. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3088-93.
REF 3 p53 Mediates epidermal growth factor (EGF) induction of MMP-2 transcription and trophoblast invasion. Placenta. 2009 Dec;30(12):1029-36.
REF 4 A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res. 1995 Jul 25;23(14):2584-92.
REF 5 Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene. 2001 Jan 11;20(2):240-51.
REF 6 p53 regulates caveolin gene transcription, cell cholesterol, and growth by a novel mechanism. Biochemistry. 2000 Feb 29;39(8):1966-72.
REF 7 Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter. Mol Cell Biol. 1995 Dec;15(12):6785-93.
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 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 14 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 15 The retinoblastoma protein binds the promoter of the survival gene bcl-2 and regulates its transcription in epithelial cells through transcription factor AP-2. Mol Cell Biol. 2002 Nov;22(22):7877-88.
REF 16 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 17 Transcription factor repression and activation of the human acetylcholinesterase gene. J Biol Chem. 1995 Oct 6;270(40):23511-9.
REF 18 Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation. EMBO J. 1997 Feb 17;16(4):750-9.
REF 19 The human Pim-1 gene is selectively transcribed in different hemato-lymphoid cell lines in spite of a G + C-rich housekeeping promoter. Mol Cell Biol. 1990 Apr;10(4):1680-8.
REF 20 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 21 The proximal promoter region of the gene encoding human 17beta-hydroxysteroid dehydrogenase type 1 contains GATA, AP-2, and Sp1 response elements: analysis of promoter function in choriocarcinoma cells. Endocrinology. 1997 Aug;138(8):3417-25.
REF 22 AP-2-mediated regulation of human NAD(P)H: quinone oxidoreductase 1 (NQO1) gene expression. Biochem Pharmacol. 1996 Mar 22;51(6):771-8.
REF 23 Cloning and functional characterization of the 5' flanking region of the human mitochondrial malic enzyme gene. Regulatory role of Sp1 and AP-2. Eur J Biochem. 2001 May;268(10):3017-27.
REF 24 Transcriptional regulation of the human neuropeptide Y gene by nerve growth factor. J Biol Chem. 1994 Jun 3;269(22):15460-8.

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