ࡱ > a { jbjb ^ } V V V V $ B f= f= f= P = j> B x *B K K K K yM yM yM w w w w w w w , y R +| x yM uM yM yM yM x uk V V K K x uk uk uk yM V R K K w uk V V V V yM w uk uk k S " l B 䇗 f= j l l x 0 x l | uk | l uk B B $9 f= B B f= Table S1: Validated TFBSs used in this study.
Target geneExperimental supportTP53 binding sitesADARB1ADARB1 was upregulated in a TP53-dependent manner after UV exposure, and RE functionality was confirmed using yeast reporter assays as well as luciferase reporter assays in human cells ADDIN EN.CITE Tomso20055905915843459102182005May 3Functionally distinct polymorphic sequences in the human genome that are targets for p53 transactivation6431-6Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.Tomso, D. J.Inga, A.Menendez, D.Pittman, G. S.Campbell, M. R.Storici, F.Bell, D. A.Resnick, M. A.Proc Natl Acad Sci U S ABase SequenceCell Line, TumorComparative StudyComputational BiologyDNA, Complementary/genetics*Gene Expression Regulation*Genome, HumanHumansLuciferasesMutagenesis, Site-DirectedPlasmids/geneticsPolymorphism, Single Nucleotide/geneticsPromoter Regions (Genetics)/geneticsResponse Elements/geneticsReverse Transcriptase Polymerase Chain ReactionSequence AlignmentTrans-Activation (Genetics)/*geneticsTransfectionTumor Suppressor Protein p53/genetics/*metabolismYeastshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15843459[1].APAF1APAF1 expression is induced in a TP53-dependent fashion following exposure to camptothecin in human neurons, and the functional RE was identified using EMSA and luciferase assays ADDIN EN.CITE Fortin2001630631159173015522001Oct 15APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death207-16Ottawa Health Research Institute - Neuroscience, University of Ottawa, Ottawa, Ontario K1H-8M5, Canada.Fortin, A.Cregan, S. P.MacLaurin, J. G.Kushwaha, N.Hickman, E. S.Thompson, C. S.Hakim, A.Albert, P. R.Cecconi, F.Helin, K.Park, D. S.Slack, R. S.J Cell BiolAnimals*ApoptosisBase SequenceBrain Ischemia/metabolism/pathologyCamptothecin/pharmacologyCell LineCells, CulturedMiceMice, TransgenicNeurons/*metabolism/pathologyPromoter Regions (Genetics)Protein BiosynthesisProteins/*genetics/physiologyRNA, Messenger/biosynthesisResearch Support, Non-U.S. Gov't*Trans-Activation (Genetics)Tumor Suppressor Protein p53/*physiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11591730[2]. ARHGEF7ARHGEF7 was upregulated in a TP53-dependent manner after UV exposure, and RE functionality was confirmed using yeast reporter assays as well as luciferase reporter assays in human cells ADDIN EN.CITE Tomso20055905915843459102182005May 3Functionally distinct polymorphic sequences in the human genome that are targets for p53 transactivation6431-6Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.Tomso, D. J.Inga, A.Menendez, D.Pittman, G. S.Campbell, M. R.Storici, F.Bell, D. A.Resnick, M. A.Proc Natl Acad Sci U S ABase SequenceCell Line, TumorComparative StudyComputational BiologyDNA, Complementary/genetics*Gene Expression Regulation*Genome, HumanHumansLuciferasesMutagenesis, Site-DirectedPlasmids/geneticsPolymorphism, Single Nucleotide/geneticsPromoter Regions (Genetics)/geneticsResponse Elements/geneticsReverse Transcriptase Polymerase Chain ReactionSequence AlignmentTrans-Activation (Genetics)/*geneticsTransfectionTumor Suppressor Protein p53/genetics/*metabolismYeastshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15843459[1].ATF3ATF3 was induced in a TP53-dependent manner following exposure to a variety of stresses in human cells. The RE was confirmed using EMSA and luciferase assays in human osteosarcoma cell lines ADDIN EN.CITE Zhang2002410411237243029752002Oct 11Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p531302-10Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, 113-8510, Bunkyo-ku, Tokyo, Japan.Zhang, C.Gao, C.Kawauchi, J.Hashimoto, Y.Tsuchida, N.Kitajima, S.Biochem Biophys Res CommunActivating Transcription Factor 3AllelesBlotting, WesternCysteine EndopeptidasesCysteine Proteinase Inhibitors/pharmacologyGenes, ReporterGenes, p53/*geneticsHumansLeupeptins/pharmacologyModels, GeneticMultienzyme Complexes/antagonists & inhibitorsMutationPlasmids/metabolismPromoter Regions (Genetics)Proteasome Endopeptidase ComplexProtein BindingRNA, Messenger/metabolismResearch Support, Non-U.S. Gov'tReverse Transcriptase Polymerase Chain ReactionTemperatureTime Factors*Trans-Activation (Genetics)Transcription Factors/*metabolismTranscription, GeneticTransfectionTumor Cells, CulturedTumor Suppressor Protein p53/*metabolismUltraviolet Rayshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12372430[3]. The RE region was physically associated with TP53 in chromatin immunoprecipitation assays ADDIN EN.CITE Jen2005370371614093365172005Sep 1Identification of novel p53 target genes in ionizing radiation response7666-73Department of Pediatrics, University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.Jen, K. Y.Cheung, V. G.Cancer ResAtaxia Telangiectasia/genetics/pathologyBinding SitesCell LineChromatin ImmunoprecipitationGene Expression Regulation/*radiation effectsHumansLymphoid Tissue/cytologyProtein Binding/radiation effectsResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Response Elements/radiation effectsTrans-Activation (Genetics)/radiation effectsTumor Suppressor Protein p53/*genetics/metabolism/radiation effectshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16140933[4].BAXThe RE region was physically associated with TP53 in chromatin immunoprecipitation assays ADDIN EN.CITE Jen2005370371614093365172005Sep 1Identification of novel p53 target genes in ionizing radiation response7666-73Department of Pediatrics, University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.Jen, K. Y.Cheung, V. G.Cancer ResAtaxia Telangiectasia/genetics/pathologyBinding SitesCell LineChromatin ImmunoprecipitationGene Expression Regulation/*radiation effectsHumansLymphoid Tissue/cytologyProtein Binding/radiation effectsResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Response Elements/radiation effectsTrans-Activation (Genetics)/radiation effectsTumor Suppressor Protein p53/*genetics/metabolism/radiation effectshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16140933[4]. RE function was confirmed using luciferase assays in human cell lines using both wild-type and mutant versions of TP53 ADDIN EN.CITE Kato2003107010712826609100142003Jul 8Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis8424-9Department of Clinical Oncology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575, Japan.Kato, S.Han, S. Y.Liu, W.Otsuka, K.Shibata, H.Kanamaru, R.Ishioka, C.Proc Natl Acad Sci U S A*Amino Acid SubstitutionDNA RepairGenes, Reporter*Genes, p53HumansLuciferases/analysis/geneticsModels, MolecularMutagenesis, Site-DirectedMutation, MissensePoint MutationPolymerase Chain ReactionProtein ConformationProtein Structure, TertiaryRecombinant Fusion Proteins/physiologyResearch Support, Non-U.S. Gov'tSaccharomyces cerevisiae/geneticsStructure-Activity RelationshipTrans-Activation (Genetics)Tumor Suppressor Protein p53/chemistry/*physiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12826609[5].BBC3BBC3 is induced following TP53 activation, and the functional RE was verified by EMSA assays ADDIN EN.CITE Nakano20017007011463392732001MarPUMA, a novel proapoptotic gene, is induced by p53683-94Regulation of Cell Growth Laboratory, National Cancer Institute at Frederick, Maryland 21702, USA.Nakano, K.Vousden, K. H.Mol CellAlternative Splicing/geneticsAmino Acid Sequence*ApoptosisBase SequenceBinding SitesCaspases/metabolism*Cell Cycle ProteinsCell DivisionCell LineCloning, MolecularCytochrome c Group/metabolismDNA/genetics/metabolismEnzyme ActivationEnzyme Precursors/metabolismExons/genetics*Helminth ProteinsHumansIntrons/geneticsMitochondria/chemistry/metabolismMolecular Sequence DataNuclear Proteins/chemistry/genetics/*metabolismProtein BindingProto-Oncogene Proteins c-bcl-2/metabolismRNA, Messenger/genetics/metabolism*Trans-Activation (Genetics)Tumor Cells, CulturedTumor Suppressor Protein p53/*metabolismhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11463392Yu2003710711257449910042003Feb 18PUMA mediates the apoptotic response to p53 in colorectal cancer cells1931-6The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA.Yu, J.Wang, Z.Kinzler, K. W.Vogelstein, B.Zhang, L.Proc Natl Acad Sci U S AApoptosis/*geneticsBase SequenceColorectal Neoplasms/*pathologyDNA PrimersGene TargetingHumansProto-Oncogene Proteins/physiology*Proto-Oncogene Proteins c-bcl-2Research Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Tumor Suppressor Protein p53/*physiologybcl-2-Associated X Proteinhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12574499Jeffers20037207214585359442003OctPuma is an essential mediator of p53-dependent and -independent apoptotic pathways321-8St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.Jeffers, J. R.Parganas, E.Lee, Y.Yang, C.Wang, J.Brennan, J.MacLean, K. H.Han, J.Chittenden, T.Ihle, J. N.McKinnon, P. J.Cleveland, J. L.Zambetti, G. P.Cancer CellAnimalsApoptosis/*physiology/radiation effectsApoptosis Regulatory ProteinsCytokines/metabolismMiceMice, KnockoutMicroscopy, FluorescenceProto-Oncogene Proteins/genetics/*metabolismProto-Oncogene Proteins c-myc/metabolismRadiation, IonizingResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Signal Transduction/*physiologyT-Lymphocytes/immunology/metabolismTumor Suppressor Protein p53/genetics/*metabolismhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14585359[6-8]. The RE region was also physically associated with TP53 in chromatin immunoprecipitation assays ADDIN EN.CITE Jen2005370371614093365172005Sep 1Identification of novel p53 target genes in ionizing radiation response7666-73Department of Pediatrics, University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.Jen, K. Y.Cheung, V. G.Cancer ResAtaxia Telangiectasia/genetics/pathologyBinding SitesCell LineChromatin ImmunoprecipitationGene Expression Regulation/*radiation effectsHumansLymphoid Tissue/cytologyProtein Binding/radiation effectsResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Response Elements/radiation effectsTrans-Activation (Genetics)/radiation effectsTumor Suppressor Protein p53/*genetics/metabolism/radiation effectshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16140933[4]. BIDBID is induced in a TP53-dependent manner in irradiated mice and the functional RE was identified in human cells using EMSA, luciferase, and chromatin immunoprecipitation assays ADDIN EN.CITE Sax200262062124020424112002NovBID regulation by p53 contributes to chemosensitivity842-9Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.Sax, J. K.Fei, P.Murphy, M. E.Bernhard, E.Korsmeyer, S. J.El-Deiry, W. S.Nat Cell BiolAdenoviridae/geneticsAnimalsAnnexin A5/pharmacologyApoptosisBH3 Interacting Domain Death Agonist ProteinBlotting, NorthernBlotting, WesternCarrier Proteins/biosynthesis/*physiologyCell DeathCell LineCell SeparationChromatin/metabolismColon/metabolismColoring Agents/pharmacologyDNA DamageDNA, Complementary/metabolismDoxorubicin/pharmacologyEpithelium/metabolismFemaleFibroblasts/metabolismFlow CytometryFluorouracil/pharmacologyGamma Rays*Gene Expression RegulationHumansIn Situ HybridizationLuciferases/metabolismMiceModels, GeneticOligonucleotide Array Sequence AnalysisPlasmids/metabolismPrecipitin TestsProtein ConformationRNA, Messenger/metabolismResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Spleen/metabolismTemperatureTranscription, GeneticTumor Suppressor Protein p53/*physiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12402042[9].BTG2BTG2s antiproliferative activity was confirmed using transformation assays in NIH3T3 cells. BTG2 induction was observed in a TP53-dependent manner following irradiation. RE function was verified using b- g a l a c t o s i d a s e r e p o r t e r A D D I N E N . C I T E <