IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ http://www.ebi.ac.uk/ vaseva-2012-1 p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis. human-hct116 Human colon carcinoma HCT116 cells hct116 Human colon carcinoma line HCT116 anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M. Apoptosis - Interactions involving proteins with a function related to apoptosis ute.moll@sbumed.org umoll@notes.cc.sunysb.edu Cell (0092-8674) 2012 Only protein-protein interactions imex curation vaseva-2012-3 p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis. in vitro In vitro pull down pull down western blot western blot Immuno blot Immuno blot Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M. Apoptosis - Interactions involving proteins with a function related to apoptosis ute.moll@sbumed.org umoll@notes.cc.sunysb.edu Cell (0092-8674) 2012 Only protein-protein interactions imex curation vaseva-2012-2 p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis. human-hct116 Human colon carcinoma HCT116 cells hct116 Human colon carcinoma line HCT116 anti tag coip anti tag coimmunoprecipitation anti tag coip western blot western blot Immuno blot Immuno blot Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M. Apoptosis - Interactions involving proteins with a function related to apoptosis ute.moll@sbumed.org umoll@notes.cc.sunysb.edu Cell (0092-8674) 2012 Only protein-protein interactions imex curation vaseva-2012-4 p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis. rat-c6 Rattus norvegicus c6 Rat glial tumour fluorescence imaging fluorescence microscopy fluorescence imaging immunostaining immunostaining Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M. Apoptosis - Interactions involving proteins with a function related to apoptosis ute.moll@sbumed.org umoll@notes.cc.sunysb.edu Cell (0092-8674) 2012 Only protein-protein interactions imex curation vaseva-2012-5 p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis. mouse-embryonic_fibroblast Mus musculus embryonic fibroblasts embryonic_fibroblast Embryonic fibroblast Fibroblasts taken from an embryonic as opposed to a foetal or adult source. Foetus is defined as the stage at which tissue diferentiation is initiated. Tissue taken from an embryonic as opposed to a foetal or adult source. Embryo is defined as the development stage prior to organ formation. anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M. Apoptosis - Interactions involving proteins with a function related to apoptosis ute.moll@sbumed.org umoll@notes.cc.sunysb.edu Cell (0092-8674) 2012 Only protein-protein interactions imex curation vaseva-2012-6 p53 Opens the Mitochondrial Permeability Transition Pore to Trigger Necrosis. mouse-brain Mus musculus brain brain Brain [cerebrum] anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M. Apoptosis - Interactions involving proteins with a function related to apoptosis ute.moll@sbumed.org umoll@notes.cc.sunysb.edu Cell (0092-8674) 2012 Only protein-protein interactions imex curation p53_human Cellular tumor antigen p53 TP53 P53 Tumor suppressor p53 Phosphoprotein p53 Antigen NY-CO-13 protein protein human Homo sapiens Human MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD ppif_human Peptidyl-prolyl cis-trans isomerase F, mitochondrial PPIF CYP3 Cyclophilin F Rotamase F Cyclophilin D Mitochondrial cyclophilin protein protein human Homo sapiens Human MLALRCGSRWLGLLSVPRSVPLRLPAARACSKGSGDPSSSSSSGNPLVYLDVDANGKPLGRVVLELKADVVPKTAENFRALCTGEKGFGYKGSTFHRVIPSFMCQAGDFTNHNGTGGKSIYGSRFPDENFTLKHVGPGVLSMANAGPNTNGSQFFICTIKTDWLDGKHVVFGHVKEGMDVVKKIESFGSKSGRTSKKIVITDCGQLS grp75_human Stress-70 protein, mitochondrial HSPA9 GRP75 HSPA9B 75 kDa glucose-regulated protein Heat shock 70 kDa protein 9 Peptide-binding protein 74 Mortalin mt-HSP70 protein protein human Homo sapiens Human MISASRAAAARLVGAAASRGPTAARHQDSWNGLSHEAFRLVSRRDYASEAIKGAVVGIDLGTTNSCVAVMEGKQAKVLENAEGARTTPSVVAFTADGERLVGMPAKRQAVTNPNNTFYATKRLIGRRYDDPEVQKDIKNVPFKIVRASNGDAWVEAHGKLYSPSQIGAFVLMKMKETAENYLGHTAKNAVITVPAYFNDSQRQATKDAGQISGLNVLRVINEPTAAALAYGLDKSEDKVIAVYDLGGGTFDISILEIQKGVFEVKSTNGDTFLGGEDFDQALLRHIVKEFKRETGVDLTKDNMALQRVREAAEKAKCELSSSVQTDINLPYLTMDSSGPKHLNMKLTRAQFEGIVTDLIRRTIAPCQKAMQDAEVSKSDIGEVILVGGMTRMPKVQQTVQDLFGRAPSKAVNPDEAVAIGAAIQGGVLAGDVTDVLLLDVTPLSLGIETLGGVFTKLINRNTTIPTKKSQVFSTAADGQTQVEIKVCQGEREMAGDNKLLGQFTLIGIPPAPRGVPQIEVTFDIDANGIVHVSAKDKGTGREQQIVIQSSGGLSKDDIENMVKNAEKYAEEDRRKKERVEAVNMAEGIIHDTETKMEEFKDQLPADECNKLKEEISKMRELLARKDSETGENIRQAASSLQQASLKLFEMAYKKMASEREGSGSSGTGEQKEDQKEEKQ ch60_human 60 kDa heat shock protein, mitochondrial HSPD1 HSP60 Heat shock protein 60 60 kDa chaperonin Chaperonin 60 Mitochondrial matrix protein P1 P60 lymphocyte protein HuCHA60 protein protein human Homo sapiens Human MLRLPTVFRQMRPVSRVLAPHLTRAYAKDVKFGADARALMLQGVDLLADAVAVTMGPKGRTVIIEQSWGSPKVTKDGVTVAKSIDLKDKYKNIGAKLVQDVANNTNEEAGDGTTTATVLARSIAKEGFEKISKGANPVEIRRGVMLAVDAVIAELKKQSKPVTTPEEIAQVATISANGDKEIGNIISDAMKKVGRKGVITVKDGKTLNDELEIIEGMKFDRGYISPYFINTSKGQKCEFQDAYVLLSEKKISSIQSIVPALEIANAHRKPLVIIAEDVDGEALSTLVLNRLKVGLQVVAVKAPGFGDNRKNQLKDMAIATGGAVFGEEGLTLNLEDVQPHDLGKVGEVIVTKDDAMLLKGKGDKAQIEKRIQEIIEQLDVTTSEYEKEKLNERLAKLSDGVAVLKVGGTSDVEVNEKKDRVTDALNATRAAVEEGIVLGGGCALLRCIPALDSLTPANEDQKIGIEIIKRTLKIPAMTIAKNAGVEGSLIVEKIMQSSSEVGYDAMAGDFVNMVEKGIIDPTKVVRTALLDAAGVASLLTTAEVVVTEIPKEEKDPGMGAMGGMGGGMGGGMF p53_rat Cellular tumor antigen p53 Tp53 P53 Tumor suppressor p53 protein protein rat Rattus norvegicus (Rat) Rat MEDSQSDMSIELPLSQETFSCLWKLLPPDDILPTTATGSPNSMEDLFLPQDVAELLEGPEEALQVSAPAAQEPGTEAPAPVAPASATPWPLSSSVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSISLNKLFCQLAKTCPVQLWVTSTPPPGTRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNPYAEYLDDRQTFRHSVVVPYEPPEVGSDYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEEHCPELPPGSAKRALPTSTSSSPQQKKKPLDGEYFTLKIRGRERFEMFRELNEALELKDARAAEESGDSRAHSSYPKTKKGQSTSRHKKPMIKKVGPDSD ppif_rat Peptidyl-prolyl cis-trans isomerase F, mitochondrial Cyclophilin D Ppif Cyclophilin F Rotamase F protein protein rat Rattus norvegicus (Rat) Rat MLALRCGPRLLGLLSGPRSAPLLLSTTRTCSDGGARGANSSSQNPLVYLDVGADGQPLGRVVLELKADVVPKTAENFRALCTGEKGFGYKGSTFHRVIPAFMCQAGDFTNHNGTGGKSIYGSRFPDENFTLKHVGPGVLSMANAGPNTNGSQFFICTIKTDWLDGKHVVFGHVKEGMDVVKKIESFGSKSGKTSKKIVITDCGQLS p53_mouse Cellular tumor antigen p53 Tp53 P53 Trp53 Tumor suppressor p53 protein protein mouse Mus musculus Mouse MTAMEESQSDISLELPLSQETFSGLWKLLPPEDILPSPHCMDDLLLPQDVEEFFEGPSEALRVSGAPAAQDPVTETPGPVAPAPATPWPLSSFVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSPPLNKLFCQLAKTCPVQLWVSATPPAGSRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNLYPEYLEDRQTFRHSVVVPYEPPEAGSEYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVLCPELPPGSAKRALPTCTSASPPQKKKPLDGEYFTLKIRGRKRFEMFRELNEALELKDAHATEESGDSRAHSSYLKTKKGQSTSRHKKTMVKKVGPDSD ppif_mouse Peptidyl-prolyl cis-trans isomerase F, mitochondrial Cyclophilin D Ppif Cyclophilin F Rotamase F protein protein mouse Mus musculus Mouse MLALRCGPRLLGLLSGPRSAPLLLSATRTCSDGGARGANSSSGNPLVYLDVGADGQPLGRVVLELKADVVPKTAENFRALCTGEKGFGYKGSTFHRVIPAFMCQAGDFTNHNGTGGRSIYGSRFPDENFTLKHVGPGVLSMANAGPNTNGSQFFICTIKTDWLDGKHVVFGHVKEGMDVVKKIESFGSKSGKTSKKIVITDCGQLS tp53-ppid-1 1301053 n/a 1301059 unspecified role unspecified role bait bait n/a 1301060 unspecified role unspecified role prey prey physical association physical association false false false Fig. 2A tp53-hspa9 1301053 n/a 1301059 unspecified role unspecified role bait bait n/a 1301061 unspecified role unspecified role prey prey n/a 1301062 unspecified role unspecified role prey prey association association false false false Supp. Fig. 3D ppif-tp53 1301054 n/a 1301059 unspecified role unspecified role prey prey region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false human-hct116 Human colon carcinoma HCT116 cells hct116 Human colon carcinoma line HCT116 n/a 1301060 unspecified role unspecified role bait bait region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false physical association physical association false false false Fig. 2C, 2E, Supp. Fig. 2A-D Cyclosporin A The contact domains on p53 required for direct interaction with BclxL/Bcl2 proteins (122-134, 135-141, 173-187, 239-248) are not required for interaction with CypD. ppif-tp53 1301054 n/a 1301060 unspecified role unspecified role bait bait region gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false n/a 1301059 unspecified role unspecified role prey prey purified purified c-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range false undefined mutation mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false certain certain sequence position certain certain certain sequence position certain false certain certain sequence position certain certain certain sequence position certain false certain certain sequence position certain certain certain sequence position certain false P04637:p.Cys229Lys mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. direct interaction direct interaction false false false Fig. 2D, 2F Tetrameric p53 is the preferred partner for CypD interaction over monomeric (KEEK, for F341K, L344E, L348E, A355K) or dimeric (L229K) p53 mutants Cyclosporin A ppif-tp53 1301055 n/a 1301060 unspecified role unspecified role bait bait n/a 1301059 unspecified role unspecified role prey prey region ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false physical association physical association false false false Fig. 2B ppid-ppif 1301056 n/a 1301063 unspecified role unspecified role neutral component neutral component n/a 1301064 unspecified role unspecified role neutral component neutral component colocalization colocalization false false false Fig. 3C Hydrogen peroxide ppif-tp53 1301057 n/a 1301065 unspecified role unspecified role prey prey n/a 1301066 unspecified role unspecified role bait bait physical association physical association false false false Supp. Fig. 6H Interaction observed in Bax-/-, Bak-/- cells. ppif-tp53 1301058 n/a 1301065 unspecified role unspecified role prey prey n/a 1301066 unspecified role unspecified role bait bait physical association physical association false false false Fig. 7C A pathologic p53-CypD complex was induced in infarcted brains after controlled unilateral acute middle cerebral artery occlusion. Induced p53-CypD complex was undetectable in CsA-pretreated, stroke-protected control mice. The complex was only barely detectable in p53+/− mice, whose stroke stress-mediated p53 induction did not exceed the baseline p53 levels of control mice, and which were also strongly protected from infarction, supporting the idea that this p53-CypD axis is an important pathophysiologic contributor to ischemic stroke.