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/ Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J. Biol. Chem. (0021-9258) 2007 imex curation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp 27-Aug-2008: Contacted by JYOTI. davet Only protein-protein interactions chlae-cos_7 Cercopithecus aethiops simian cells transformed with SV40 Grivet cos_7 cercopithecus aethiops, by transformation with SV40 2 hybrid two hybrid 2H 2h Gal4 transcription regeneration two-hybrid yeast two hybrid 2-hybrid classical two hybrid classical two hybrid 2H two-hybrid 2-hybrid Gal4 transcription regeneration 2h yeast two hybrid Y2H Y-2H 2 hybrid predetermined predetermined participant predetermined Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp Accepted 2008-JUL-2 by DAVET. 27-Aug-2008: Contacted by JYOTI. J. Biol. Chem. (0021-9258) 2007 davet Only protein-protein interactions imex curation Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J. Biol. Chem. (0021-9258) 2007 imex curation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp 27-Aug-2008: Contacted by JYOTI. davet Only protein-protein interactions human-lncap Human caucasian prostate carcinoma lncap Human caucasian prostate adenocarcinoma anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp Accepted 2008-JUL-2 by DAVET. J. Biol. Chem. (0021-9258) 2007 davet Only protein-protein interactions imex curation Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J. Biol. Chem. (0021-9258) 2007 imex curation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp 27-Aug-2008: Contacted by JYOTI. davet Only protein-protein interactions human-lncap Human caucasian prostate carcinoma lncap Human caucasian prostate adenocarcinoma ch-ip chromatin immunoprecipitation assay ch-ip primer specific pcr primer specific pcr Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp Accepted 2008-JUL-2 by DAVET. 27-Aug-2008: Contacted by JYOTI. J. Biol. Chem. (0021-9258) 2007 davet Only protein-protein interactions imex curation Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J. Biol. Chem. (0021-9258) 2007 imex curation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp 27-Aug-2008: Contacted by JYOTI. davet Only protein-protein interactions mouse-3t3_l1 Mus musculus embryonic cells Fibroblast-like. Adipose like when confluent 3t3_l1 Mouse embryo cells Fibroblast-like. Adipose like when confluent confocal microscopy confocal microscopy tag visualisation tag visualisation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp Accepted 2008-JUL-2 by DAVET. 27-Aug-2008: Contacted by JYOTI. J. Biol. Chem. (0021-9258) 2007 davet Only protein-protein interactions imex curation Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J. Biol. Chem. (0021-9258) 2007 imex curation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp 27-Aug-2008: Contacted by JYOTI. davet Only protein-protein interactions chlae-cos_7 Cercopithecus aethiops simian cells transformed with SV40 Grivet cos_7 cercopithecus aethiops, by transformation with SV40 confocal microscopy confocal microscopy tag visualisation tag visualisation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp Accepted 2008-JUL-2 by DAVET. 27-Aug-2008: Contacted by JYOTI. J. Biol. Chem. (0021-9258) 2007 davet Only protein-protein interactions imex curation Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. Insulin-like growth factor 1/insulin signaling activates androgen signaling through direct interactions of Foxo1 with androgen receptor. J. Biol. Chem. (0021-9258) 2007 imex curation Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp 27-Aug-2008: Contacted by JYOTI. davet Only protein-protein interactions chlae-cos_7 Cercopithecus aethiops simian cells transformed with SV40 Grivet cos_7 cercopithecus aethiops, by transformation with SV40 1 hybrid one hybrid yeast one-hybrid yeast one hybrid one-hybrid 1 hybrid yeast one-hybrid one-hybrid yeast one hybrid predetermined predetermined participant predetermined Fan W., Yanase T., Morinaga H., Okabe T., Nomura M., Daitoku H., Fukamizu A., Kato S., Takayanagi R., Nawata H. Cancer - Interactions investigated in the context of cancer The LNCaP cells used were transfected with PTEN (human phosphatase and tensin homolog). yanase@intmed3.med.kyushu-u.ac.jp Accepted 2008-JUL-2 by DAVET. 27-Aug-2008: Contacted by JYOTI. J. Biol. Chem. (0021-9258) 2007 davet Only protein-protein interactions imex curation andr_mouse Androgen receptor Ar Nr3c4 Dihydrotestosterone receptor Nuclear receptor subfamily 3 group C member 4 protein protein mouse Mus musculus Mouse MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREAIQNPGPRHPEAANIAPPGACLQQRQETSPRRRRRQQHTEDGSPQAHIRGPTGYLALEEEQQPSQQQAASEGHPESSCLPEPGAATAPGKGLPQQPPAPPDQDDSAAPSTLSLLGPTFPGLSSCSADIKDILNEAGTMQLLQQQQQQQQHQQQHQQHQQQQEVISEGSSARAREATGAPSSSKDSYLGGNSTISDSAKELCKAVSVSMGLGVEALEHLSPGEQLRGDCMYASLLGGPPAVRPTPCAPLPECKGLPLDEGPGKSTEETAEYSSFKGGYAKGLEGESLGCSGSSEAGSSGTLEIPSSLSLYKSGALDEAAAYQNRDYYNFPLALSGPPHPPPPTHPHARIKLENPLDYGSAWAAAAAQCRYGDLGSLHGGSVAGPSTGSPPATTSSSWHTLFTAEEGQLYGPGGGGGSSSPSDAGPVAPYGYTRPPQGLTSQESDYSASEVWYPGGVVNRVPYPSPNCVKSEMGPWMENYSGPYGDMRLDSTRDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGENSNAGSPTEDPSQKMTVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIYFHTQ DIP protein P19091 original sequence version: 136 FD9EE07C07F7A568 klk3_human_gene Human kallikrein-related peptidase 3 (KLK3) (PSA) gene gene human Homo sapiens Human foxo1_mouse Forkhead box protein O1 Foxo1 Fkhr Foxo1a Forkhead box protein O1A Forkhead in rhabdomyosarcoma protein protein mouse Mus musculus Mouse MAEAPQVVETDPDFEPLPRQRSCTWPLPRPEFNQSNSTTSSPAPSGGAAANPDAAASLASASAVSTDFMSNLSLLEESEDFARAPGCVAVAAAAAASRGLCGDFQGPEAGCVHPAPPQPPPTGPLSQPPPVPPSAAAAAGPLAGQPRKTSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWMLNPEGGKSGKSPRRRAASMDNNSKFAKSRGRAAKKKASLQSGQEGPGDSPGSQFSKWPASPGSHSNDDFDNWSTFRPRTSSNASTISGRLSPIMTEQDDLGDGDVHSLVYPPSAAKMASTLPSLSEISNPENMENLLDNLNLLSSPTSLTVSTQSSPGSMMQQTPCYSFAPPNTSLNSPSPNYSKYTYGQSSMSPLPQMPMQTLQDSKSSYGGLNQYNCAPGLLKELLTSDSPPHNDIMSPVDPGVAQPNSRVLGQNVMMGPNSVMPAYGSQASHNKMMNPSSHTHPGHAQQTASVNGRTLPHVVNTMPHTSAMNRLTPVKTPLQVPLSHPMQMSALGSYSSVSSCNGYGRMGVLHQEKLPSDLDGMFIERLDCDMESIIRNDLMDGDTLDFNFDNVLPNQSFPHSVKTTTHSWVSG 3FF58636EA85205F foxo1_human Forkhead box protein O1 FOXO1 FKHR FOXO1A Forkhead box protein O1A Forkhead in rhabdomyosarcoma protein protein human Homo sapiens Human MAEAPQVVEIDPDFEPLPRPRSCTWPLPRPEFSQSNSATSSPAPSGSAAANPDAAAGLPSASAAAVSADFMSNLSLLEESEDFPQAPGSVAAAVAAAAAAAATGGLCGDFQGPEAGCLHPAPPQPPPPGPLSQHPPVPPAAAGPLAGQPRKSSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWMLNPEGGKSGKSPRRRAASMDNNSKFAKSRSRAAKKKASLQSGQEGAGDSPGSQFSKWPASPGSHSNDDFDNWSTFRPRTSSNASTISGRLSPIMTEQDDLGEGDVHSMVYPPSAAKMASTLPSLSEISNPENMENLLDNLNLLSSPTSLTVSTQSSPGTMMQQTPCYSFAPPNTSLNSPSPNYQKYTYGQSSMSPLPQMPIQTLQDNKSSYGGMSQYNCAPGLLKELLTSDSPPHNDIMTPVDPGVAQPNSRVLGQNVMMGPNSVMSTYGSQASHNKMMNPSSHTHPGHAQQTSAVNGRPLPHTVSTMPHTSGMNRLTQVKTPVQVPLPHPMQMSALGGYSSVSSCNGYGRMGLLHQEKLPSDLDGMFIERLDCDMESIIRNDLMDGDTLDFNFDNVLPNQSFPHSVKTTTHSWVSG DIP protein Q12778 original sequence version: 132 DIP protein Q12778 original sequence version: 84 6DEF6C994BDFDBAB andr_human Androgen receptor Dihydrotestosterone receptor Nuclear receptor subfamily 3 group C member 4 AR DHTR NR3C4 protein protein human Homo sapiens Human MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQQQQQQQQQQQQQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQSALECHPERGCVPEPGAAVAASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSADLKDILSEASTMQLLQQQQQEAVSEGSSSGRAREASGAPTSSKDNYLGGTSTISDNAKELCKAVSVSMGLGVEALEHLSPGEQLRGDCMYAPLLGVPPAVRPTPCAPLAECKGSLLDDSAGKSTEDTAEYSPFKGGYTKGLEGESLGCSGSAAAGSSGTLELPSTLSLYKSGALDEAAAYQSRDYYNFPLALAGPPPPPPPPHPHARIKLENPLDYGSAWAAAAAQCRYGDLASLHGAGAAGPGSGSPSAAASSSWHTLFTAEEGQLYGPCGGGGGGGGGGGGGGGGGGGGGGGEAGAVAPYGYTRPPQGLAGQESDFTAPDVWYPGGMVSRVPYPSPTCVKSEMGPWMDSYSGPYGDMRLETARDHVLPIDYYFPPQKTCLICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLGARKLKKLGNLKLQEEGEASSTTSPTEETTQKLTVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAALLSSLNELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELDRIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIYFHTQ DIP protein P10275 original sequence version: 220 DIP protein P10275-1 original sequence version: 213 DIP protein P10275 original sequence version: 216 DIP protein P10275 original sequence version: 143 DIP protein P10275 original sequence version: 174 DIP protein P10275 original sequence version: 169 DIP protein P10275 original sequence version: 188 DIP protein P10275-1 original sequence version: 188 DIP protein P10275 original sequence version: 196 DIP protein P10275 original sequence version: 217 DIP protein P10275-1 original sequence version: 217 DIP protein P10275-1 original sequence version: 207 A73432C55D39AE06 ar-foxo1 2 9 unspecified role unspecified role prey prey region flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 11 unspecified role unspecified role bait bait physical association physical association 3 A FLAG-Foxo1 bands were detected in anti-AR antibody-precipitated immune complexes from cells treated with DHT 5alpha-dihydrotestosterone (DHT) - DHT treatment of cells enhances this interaction. IGF1 or insulin treatment of cells decreased the levels of this interaction but did not abolish it. P10275; Q9R1E0 transfection ar-foxo1-1 2 10 unspecified role unspecified role prey prey 11 unspecified role unspecified role bait bait physical association physical association S 5 5alpha-dihydrotestosterone (DHT) - DHT treatment of cells enhances this interaction. we further verified that endogenous AR and Foxo1 interacted in an androgen-dependent manner ar-foxo1-2 6 9 unspecified role unspecified role prey prey 11 unspecified role unspecified role bait bait physical association physical association 3 B pACT-Foxo1 (with a viral VP16 activation domain fused to the Foxo1 N terminus) enhanced the liganded AR function This interaction is inhibited by the presence of FLAG-Foxo1. 5alpha-dihydrotestosterone (DHT) - This interaction was enhanced by treatment of cells with DHT. Insulin - This interaction was enhanced by treatment of cells with insulin. ar-foxo1-3 1 9 unspecified role unspecified role prey prey 11 unspecified role unspecified role bait bait c-terminal sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain physical association physical association Foxo1 cDNA was fused to the VP16 activation domain in either the forward (pACT-Foxo1-F) or reverse orientation (pACT-Foxo1-R); pACT-Foxo1-F, but not pACT-Foxo1-R significantly stimulated the reporter in the presence of DHT. These data indicate that the AR C terminus interacts with Foxo1 in a hormone-dependent manner. 3 D 5alpha-dihydrotestosterone (DHT) - This interaction was enhanced by treatment of cells with DHT. ar-foxo1-4 5 9 unspecified role unspecified role neutral component neutral component region EYFP yfp tag yellow fluorescent protein tag YFP yellow fluorescent protein yellow fluorescent protein YFP yfp tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 11 unspecified role unspecified role neutral component neutral component region egfp tag enhanced green fluorescent protein tag enhanced green fluorescent protein EGFP enhanced green fluorescent protein EGFP egfp tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined colocalization colocalization 4, S8 This colocalization was inhibited when cells treated with DHT (5alpha-dihydrotestosterone ) were also treated with IGF1. P10275; Q9R1E0 transfection These observations suggest that liganded AR sequestered part of the Foxo1 in the nucleus, even in the presence of IGF1. EYFP-Foxo1-3A (T24A, S253A, and S316A), an AKT non-phosphorylable mutant, is localized in the nucleus in a manner not dependent on IGF1 treatment. EYFP-Foxo1-3A disrupted formation of DHT (5alpha-dihydrotestosterone) induced AR foci and this could not be recued by IGF1 treatment. ar-foxo1-5 4 9 unspecified role unspecified role neutral component neutral component region EYFP yfp tag yellow fluorescent protein tag YFP yellow fluorescent protein yellow fluorescent protein YFP yfp tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 7 unspecified role unspecified role neutral component neutral component colocalization colocalization S 7 Q9R1E0 transfection Q9R1E0 overexpression AR foci induced by DHT (5alpha-dihydrotestosterone) treatment were reduced by Foxo1 overexpression. foxo1-klk3 3 9 unspecified role unspecified role bait bait region flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 8 unspecified role unspecified role prey prey association association 5b Occupancy of the promoter and enhancer regions of the PSA gene was increased by DHT (5alpha-dihydrotestosterone). Occupancy of the promoter and enhancer regions of the PSA gene was decreased by treatment with IGF1 or insulin. Q9R1E0 transfection ar-klk3 3 11 unspecified role unspecified role bait bait 8 unspecified role unspecified role prey prey association association 5 C Interaction of Foxo1 and AR within the human PSA promoter. Foxo1-3A (T24A, S253A, S316A), an AKT non-phosphorylable mutant, singificantly interfered with the increase of AR bound to KLK3 (PSA). This suggests that phosphorylable Foxo1 is required for the increase in AR-DNA interaction in response to IGF1 or insulin.