MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells. NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells. EMBO J. (0261-4189) 2012 imex curation Ota S., Ishitani S., Shimizu N., Matsumoto K., Itoh M., Ishitani T. Only protein-protein interactions mouse-neuro_2_a Mus musculus albino neuroblastoma cell line neuro 2 a (N2a) neuro_2_a Mouse Albino neuroblastoma neuro 2 a cell line anti bait coip anti bait coimmunoprecipitation anti bait coip predetermined predetermined participant predetermined Ota S., Ishitani S., Shimizu N., Matsumoto K., Itoh M., Ishitani T. EMBO J. (0261-4189) 2012 Only protein-protein interactions imex curation NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells. NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells. EMBO J. (0261-4189) 2012 imex curation Ota S., Ishitani S., Shimizu N., Matsumoto K., Itoh M., Ishitani T. Only protein-protein interactions rat-pc12 Rattus norvegicus PC12 cells pc12 Rat adrenal pheochromocytoma cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Ota S., Ishitani S., Shimizu N., Matsumoto K., Itoh M., Ishitani T. EMBO J. (0261-4189) 2012 Only protein-protein interactions imex curation NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells. NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells. EMBO J. (0261-4189) 2012 imex curation Ota S., Ishitani S., Shimizu N., Matsumoto K., Itoh M., Ishitani T. Only protein-protein interactions mouse-neuro_2_a Mus musculus albino neuroblastoma cell line neuro 2 a (N2a) neuro_2_a Mouse Albino neuroblastoma neuro 2 a cell line anti tag coip anti tag coimmunoprecipitation anti tag coip predetermined predetermined participant predetermined Ota S., Ishitani S., Shimizu N., Matsumoto K., Itoh M., Ishitani T. EMBO J. (0261-4189) 2012 Only protein-protein interactions imex curation hdac1_mouse Histone deacetylase 1 Hdac1 protein protein mouse Mus musculus Mouse MAQTQGTKRKVCYYYDGDVGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKANAEEMTKYHSDDYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVASAVKLNKQQTDIAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHGDGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNYPLRDGIDDESYEAIFKPVMSKVMEMFQPSAVVLQCGSDSLSGDRLGCFNLTIKGHAKCVEFVKSFNLPMLMLGGGGYTIRNVARCWTYETAVALDTEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTNEYLEKIKQRLFENLRMLPHAPGVQMQAIPEDAIPEESGDEDEEDPDKRISICSSDKRIACEEEFSDSDEEGEGGRKNSSNFKKAKRVKTEDEKEKDPEEKKEVTEEEKTKEEKPEAKGVKEEVKLA DIP protein O09106 original sequence version: 147 DIP protein O09106 original sequence version: 87 DIP protein O09106 original sequence version: 131 DIP protein O09106 original sequence version: 119 DIP protein O09106 original sequence version: 106 DIP protein O09106 original sequence version: 144 DIP protein O09106 original sequence version: 146 DIP protein O09106 original sequence version: 161 DIP protein O09106 original sequence version: 167 DIP protein O09106 original sequence version: 169 DIP protein O09106 original sequence version: 124 DIP protein O09106 original sequence version: 134 DIP protein O09106 original sequence version: 103 DIP protein O09106 original sequence version: 122 7F64D3C17F5E4844 hdac1_rat Histone deacetylase 1 Hdac1 protein protein rat Rattus norvegicus (Rat) Rat MAQTQGTKRKVCYYYDGDVGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKANAEEMTKYHSDDYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVASAVKLNKQQTDIAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHGDGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNYPLRDGIDDESYEAIFKPVMSKVMEMFQPSAVVLQCGSDSLSGDRLGCFNLTIKGHAKCVEFVKSFNLPMLMLGGGGYTIRNVARCWTYETAVALDTEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTNEYLEKIKQRLFENLRMLPHAPGVQMQAIPEDAIPEESGDEDEEDPDKRISICSSDKRIACEEEFSDSDEEGEGGRKNSSNFKKAKRVKTEDEKEKDPEEKKEVTEEEKTKEEKPEAKGVKEEVKMA Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes mint 7F6563C17F5E4844 lef1_rat Lymphoid enhancer-binding factor 1 Lef1 protein protein rat Rattus norvegicus (Rat) Rat MPQLSGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNESEIIPASNGHEVVGQTQSSQEPYHDKAREHPDDGKHPDGGLYNKGPSYSSYSGYIMMPNMNSDPYMSNGSLSPPIPRTSNKVPVVQPSHAVHPLTPLITYSDEHFSPGSHPSHIPSEVNPKQGMSRHPPAPEMPTFYPLSPGGVGQITPPLGWQGQPVYPITGGFRQAYPSSLSGDTSMSRFSHHMIPGPPGPHTTGIPHPAIVTPQVKQEHPHTDSDLMHVKPEHEQRKEQEPKRPHIKKPLNAFMLYMKEMRANVVAECTLKESAAINQILGRRWHALSREEQAKYYELARKERQLHMQLYPGWSARDNYGKKKKRKREKLQESTSGTGPRMTAAYI mint D6BEFF805CB526EA lef1_human Lymphoid enhancer-binding factor 1 LEF1 T cell-specific transcription factor 1-alpha protein protein human Homo sapiens Human MPQLSGGGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNESEIIPASNGHEVARQAQTSQEPYHDKAREHPDDGKHPDGGLYNKGPSYSSYSGYIMMPNMNNDPYMSNGSLSPPIPRTSNKVPVVQPSHAVHPLTPLITYSDEHFSPGSHPSHIPSDVNSKQGMSRHPPAPDIPTFYPLSPGGVGQITPPLGWQGQPVYPITGGFRQPYPSSLSVDTSMSRFSHHMIPGPPGPHTTGIPHPAIVTPQVKQEHPHTDSDLMHVKPQHEQRKEQEPKRPHIKKPLNAFMLYMKEMRANVVAECTLKESAAINQILGRRWHALSREEQAKYYELARKERQLHMQLYPGWSARDNYGKKKKRKREKLQESASGTGPRMTAAYI DIP protein Q9UJU2 original sequence version: 136 DIP protein Q9UJU2 original sequence version: 73 D480D440698EEFE3 ctnb1_mouse Catenin beta-1 Beta-catenin Ctnnb1 Catnb protein protein mouse Mus musculus Mouse MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEALGYRQDDPSYRSFHSGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTDL DIP protein Q02248 original sequence version: 128 DIP protein Q02248 original sequence version: 135 DIP protein Q02248 original sequence version: 147 DIP protein Q02248 original sequence version: 187 DIP protein Q02248 original sequence version: 140 D708F170A3FBED6E lef1-ctnnb1-3 3 Beta-catenin 8 western blot western blot Immuno blot Immuno blot predetermined predetermined participant predetermined unspecified role unspecified role prey prey over-expressed over expressed level over-expressed living cell living cell Beta-catenin 8 western blot western blot Immuno blot Immuno blot predetermined predetermined participant predetermined unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level LEF1 7 anti tag western anti tag western blot anti tag western predetermined predetermined participant predetermined unspecified role unspecified role bait bait over-expressed over expressed level over-expressed living cell living cell t7 tag t7 tag t7 tag MASMTGGQQMG epitope tag MASMTGGQQMG epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined association association f6a homomint mint As shown in Figure 6A, NLK overexpression had no effect on the interaction between LEF1 and b-cateninDN. hdac1-lef1 1 HDAC1 4 western blot western blot Immuno blot Immuno blot predetermined predetermined participant predetermined unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level LEF1 7 anti tag western anti tag western blot anti tag western predetermined predetermined participant predetermined unspecified role unspecified role prey prey over-expressed over expressed level over-expressed living cell living cell t7 tag t7 tag t7 tag MASMTGGQQMG epitope tag MASMTGGQQMG epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association f6b f6c mint We found that LEF1 strongly interacted with endogenous HDAC1 in neuro-2a cells and that overexpression of NLK reduced this association (Figure 6B). We also found that the non-phosphorylated form of LEF1-2A stably interacted with HDAC1 regardless of NLK overexpression. In contrast, the LEF1-2E mutant that mimics constitutive phosphorylation failed to interact with HDAC1 (Figure 6C). Thus, HDAC1 binds preferentially to the unphosphorylated form of LEF1, and this interaction is disrupted by NLK-mediated phosphorylation. hdac1-lef1-1 2 HDAC1 5 western blot western blot Immuno blot Immuno blot predetermined predetermined participant predetermined unspecified role unspecified role bait bait living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level LEF1 6 western blot western blot Immuno blot Immuno blot predetermined predetermined participant predetermined unspecified role unspecified role prey prey living cell living cell physiological level physiological level endogenous level endogenous endogenous endogenous level physical association physical association mint f8c Wnt-3a and R-spondin 3 strongly activated the TOPFLASH reporter activity, and this activation was blocked by NLK siRNA treatment (Supplementary Figure S10A), suggesting that signalling by Wnt-3a and R-spondin 3 is transduced via NLK in PC12 cells. This combined treatment induced activation of NLK kinase activity (Figure 8A), phosphorylation of Lef1 (Figure 8B), and dissociation of HDAC1 from Lef1 (Figure 8C).