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10.18632/oncotarget.5547 http://scihub22266oqcxt.onion/10.18632/oncotarget.5547 C4741501!4741501 !26474281     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 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\26474281 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Oncotarget 2015 ; 6 (33 ): 34953-67 Nephropedia Template TP {{tp|p=26474281 |t=2015. Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors |pdf=|usr=}}{{26474281 }} gab.com Text Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26474281 #FOAvip Skp1 is an essential adaptor protein of the Skp1-Cul1-F-box protein complex and is able to stabilize the conformation of some ubiquitin E3 ligases. However, the role Skp1 plays during tumorigenesis remains unclear and Skp1-targeting agent is lacking. Here we showed that Skp1 was overexpressed in 36/64 (56.3%) of non-small cell lung cancers, and elevated Skp1 was associated with poor prognosis. By structure-based high-throughput virtual screening, we found some Skp1-targeting molecules including a natural compound 6-O-angeloylplenolin (6-OAP). 6-OAP bound Skp1 at sites critical to Skp1-Skp2 interaction, leading to dissociation and proteolysis of oncogenic E3 ligases NIPA, Skp2, and ?-TRCP, and accumulation of their substrates Cyclin B1, P27 and E-Cadherin. 6-OAP induced prometaphase arrest and exerted potent anti-lung cancer activity in two murine models and showed low adverse effect. These results indicate that Skp1 is critical to lung cancer pathogenesis, and Skp1 inhibitor inactivates crucial oncogenic E3 ligases and exhibits significant therapeutic potentials. Twit Text FOAVip Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26474281 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26474281 #FOAvip English Wikipedia <ref>{{Cite pmid|26474281 }}</ref> Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors #MMPMID26474281 Liu YQ ; Wang XL ; Cheng X ; Lu YZ ; Wang GZ ; Li XC ; Zhang J ; Wen ZS ; Huang ZL ; Gao QL ; Yang LN ; Cheng YX ; Tao SC ; Liu J ; Zhou GB Oncotarget 2015[Oct]; 6 (33 ): 34953-67 PMID26474281 show ga Skp1 is an essential adaptor protein of the Skp1-Cul1-F-box protein complex and is able to stabilize the conformation of some ubiquitin E3 ligases. However, the role Skp1 plays during tumorigenesis remains unclear and Skp1-targeting agent is lacking. Here we showed that Skp1 was overexpressed in 36/64 (56.3%) of non-small cell lung cancers, and elevated Skp1 was associated with poor prognosis. By structure-based high-throughput virtual screening, we found some Skp1-targeting molecules including a natural compound 6-O-angeloylplenolin (6-OAP). 6-OAP bound Skp1 at sites critical to Skp1-Skp2 interaction, leading to dissociation and proteolysis of oncogenic E3 ligases NIPA, Skp2, and ?-TRCP, and accumulation of their substrates Cyclin B1, P27 and E-Cadherin. 6-OAP induced prometaphase arrest and exerted potent anti-lung cancer activity in two murine models and showed low adverse effect. These results indicate that Skp1 is critical to lung cancer pathogenesis, and Skp1 inhibitor inactivates crucial oncogenic E3 ligases and exhibits significant therapeutic potentials. |Aged [MESH] |Animals [MESH] |Antineoplastic Agents/chemistry/*pharmacology [MESH] |Blotting, Western [MESH] |Carcinoma, Non-Small-Cell Lung/*metabolism [MESH] |Cell Survival/drug effects [MESH] |Female [MESH] |Flow Cytometry [MESH] |Fluorescent Antibody Technique [MESH] |High-Throughput Screening Assays [MESH] |Humans [MESH] |Immunoprecipitation [MESH] |Lactones/chemistry/*pharmacology [MESH] |Lung Neoplasms/*metabolism [MESH] |Male [MESH] |Mice [MESH] |Mice, Nude [MESH] |Middle Aged [MESH] |RNA, Small Interfering [MESH] |S-Phase Kinase-Associated Proteins/analysis/antagonists & inhibitors/*biosynthesis [MESH] |Sesquiterpenes/chemistry/*pharmacology [MESH] |Transfection [MESH]Skp1 in lung cancer: clinical significance and therapeutic efficacy of(epmc).pdf DeepDyve Pubget Overpricing