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10.1038/ncomms9023 http://scihub22266oqcxt.onion/10.1038/ncomms9023 C4552080!4552080 !26310823     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26310823 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Nat+Commun 2015 ; 6 (ä): 8023 Nephropedia Template TP {{tp|p=26310823 |t=2015. Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1 |pdf=|usr=}}{{26310823 }} gab.com Text Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1 JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26310823 #FOAvip The Down syndrome-associated DYRK1A kinase has been reported as a stimulator of the developmentally important Hedgehog (Hh) pathway, but cells from Down syndrome patients paradoxically display reduced Hh signalling activity. Here we find that DYRK1A stimulates GLI transcription factor activity through phosphorylation of general nuclear localization clusters. In contrast, in vivo and in vitro experiments reveal that DYRK1A kinase can also function as an inhibitor of endogenous Hh signalling by negatively regulating ABLIM proteins, the actin cytoskeleton and the transcriptional co-activator MKL1 (MAL). As a final effector of the DYRK1A-ABLIM-actin-MKL1 sequence, we identify the MKL1 interactor Jumonji domain demethylase 1A (JMJD1A) as a novel Hh pathway component stabilizing the GLI1 protein in a demethylase-independent manner. Furthermore, a Jumonji-specific small-molecule antagonist represents a novel and powerful inhibitor of Hh signal transduction by inducing GLI1 protein degradation in vitro and in vivo. Twit Text FOAVip Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1 ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=26310823 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26310823 #FOAvip English Wikipedia <ref>{{Cite pmid|26310823 }}</ref> Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1 #MMPMID26310823 Schneider P ; Bayo-Fina JM ; Singh R ; Kumar Dhanyamraju P ; Holz P ; Baier A ; Fendrich V ; Ramaswamy A ; Baumeister S ; Martinez ED ; Lauth M Nat Commun 2015[Aug]; 6 (ä): 8023 PMID26310823 show ga The Down syndrome-associated DYRK1A kinase has been reported as a stimulator of the developmentally important Hedgehog (Hh) pathway, but cells from Down syndrome patients paradoxically display reduced Hh signalling activity. Here we find that DYRK1A stimulates GLI transcription factor activity through phosphorylation of general nuclear localization clusters. In contrast, in vivo and in vitro experiments reveal that DYRK1A kinase can also function as an inhibitor of endogenous Hh signalling by negatively regulating ABLIM proteins, the actin cytoskeleton and the transcriptional co-activator MKL1 (MAL). As a final effector of the DYRK1A-ABLIM-actin-MKL1 sequence, we identify the MKL1 interactor Jumonji domain demethylase 1A (JMJD1A) as a novel Hh pathway component stabilizing the GLI1 protein in a demethylase-independent manner. Furthermore, a Jumonji-specific small-molecule antagonist represents a novel and powerful inhibitor of Hh signal transduction by inducing GLI1 protein degradation in vitro and in vivo. |*Signal Transduction [MESH] |Actin Cytoskeleton/metabolism [MESH] |Actins [MESH] |Animals [MESH] |Cell Line, Tumor [MESH] |Down Syndrome/*metabolism [MESH] |Dyrk Kinases [MESH] |Electrophoresis, Polyacrylamide Gel [MESH] |Hedgehog Proteins/*metabolism [MESH] |Humans [MESH] |Immunoblotting [MESH] |In Vitro Techniques [MESH] |Jumonji Domain-Containing Histone Demethylases/*metabolism [MESH] |Kruppel-Like Transcription Factors/*metabolism [MESH] |Mice [MESH] |Microfilament Proteins/*metabolism [MESH] |Neoplasm Transplantation [MESH] |Polymerase Chain Reaction [MESH] |Protein Serine-Threonine Kinases/*metabolism [MESH] |Protein-Tyrosine Kinases/*metabolism [MESH] |Trans-Activators/*metabolism [MESH] |Transcription Factors/*metabolism [MESH]Identification of a novel actin-dependent signal transducing module al(epmc).pdf DeepDyve Pubget Overpricing