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10.18632/oncotarget.11511 http://scihub22266oqcxt.onion/10.18632/oncotarget.11511 C5342071!5342071 !27563826     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27563826 &cmd=llinks): Failed to open stream: HTTP request failed! 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A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct |pdf=|usr=}}{{27563826 }} gab.com Text A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27563826 #FOAvip MASTL (microtubule-associated serine/threonine kinase-like), more commonly known as Greatwall (GWL), has been proposed as a novel cancer therapy target. GWL plays a crucial role in mitotic progression, via its known substrates ENSA/ARPP19, which when phosphorylated inactivate PP2A/B55 phosphatase. When over-expressed in breast cancer, GWL induces oncogenic properties such as transformation and invasiveness. Conversely, down-regulation of GWL selectively sensitises tumour cells to chemotherapy. Here we describe the first structure of the GWL minimal kinase domain and development of a small-molecule inhibitor GKI-1 (Greatwall Kinase Inhibitor-1). In vitro, GKI-1 inhibits full-length human GWL, and shows cellular efficacy. Treatment of HeLa cells with GKI-1 reduces ENSA/ARPP19 phosphorylation levels, such that they are comparable to those obtained by siRNA depletion of GWL; resulting in a decrease in mitotic events, mitotic arrest/cell death and cytokinesis failure. Furthermore, GKI-1 will be a useful starting point for the development of more potent and selective GWL inhibitors. Twit Text FOAVip A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27563826 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27563826 #FOAvip English Wikipedia <ref>{{Cite pmid|27563826 }}</ref> A first generation inhibitor of human Greatwall kinase, enabled by structural and functional characterisation of a minimal kinase domain construct #MMPMID27563826 Ocasio CA ; Rajasekaran MB ; Walker S ; Le Grand D ; Spencer J ; Pearl FM ; Ward SE ; Savic V ; Pearl LH ; Hochegger H ; Oliver AW Oncotarget 2016[Nov]; 7 (44 ): 71182-71197 PMID27563826 show ga MASTL (microtubule-associated serine/threonine kinase-like), more commonly known as Greatwall (GWL), has been proposed as a novel cancer therapy target. GWL plays a crucial role in mitotic progression, via its known substrates ENSA/ARPP19, which when phosphorylated inactivate PP2A/B55 phosphatase. When over-expressed in breast cancer, GWL induces oncogenic properties such as transformation and invasiveness. Conversely, down-regulation of GWL selectively sensitises tumour cells to chemotherapy. Here we describe the first structure of the GWL minimal kinase domain and development of a small-molecule inhibitor GKI-1 (Greatwall Kinase Inhibitor-1). In vitro, GKI-1 inhibits full-length human GWL, and shows cellular efficacy. Treatment of HeLa cells with GKI-1 reduces ENSA/ARPP19 phosphorylation levels, such that they are comparable to those obtained by siRNA depletion of GWL; resulting in a decrease in mitotic events, mitotic arrest/cell death and cytokinesis failure. Furthermore, GKI-1 will be a useful starting point for the development of more potent and selective GWL inhibitors. |Crystallization [MESH] |HeLa Cells [MESH] |Humans [MESH] |Microtubule-Associated Proteins/*antagonists & inhibitors/chemistry [MESH] |Phosphorylation [MESH] |Protein Domains [MESH] |Protein Kinase Inhibitors/*chemical synthesis/pharmacology [MESH] |Protein Serine-Threonine Kinases/*antagonists & inhibitors/chemistry [MESH]A first generation inhibitor of human Greatwall kinase, enabled by str(epmc).pdf DeepDyve Pubget Overpricing