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10.3390/ijms19061591 http://scihub22266oqcxt.onion/10.3390/ijms19061591 C6032208!6032208!29843450     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Int+J+Mol+Sci 2018 ; 19 (6): ä Nephropedia Template TP {{tp|p=29843450|t=2018. Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development |pdf=|usr=}}{{29843450}} gab.com Text Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development JO: Int J Mol Sci http://www.kidney.de/pget.php?&tw=1&pmid=29843450 #FOAvip Transcription factors are proteins able to bind DNA and induce the transcription of specific genes. Consequently, they play a pivotal role in multiple cellular pathways and are frequently over-expressed or dysregulated in cancer. Here, we will focus on a specific ?signal transducer and activator of transcription? (STAT3) factor that is involved in several pathologies, including cancer. For long time, the mechanism by which STAT3 exerts its cellular functions has been summarized by a three steps process: (1) Protein phosphorylation by specific kinases, (2) dimerization promoted by phosphorylation, (3) activation of gene expression by the phosphorylated dimer. Consequently, most of the inhibitors reported in literature aimed at blocking phosphorylation and dimerization. However, recent observations reopened the debate and the entire functional mechanism has been revisited stimulating the scientific community to pursue new inhibition strategies. In particular, the dimerization of the unphosphorylated species has been experimentally demonstrated and specific roles proposed also for these dimers. Despite difficulties in the expression and purification of the full length STAT3, structural biology investigations allowed the determination of atomistic structures of STAT3 dimers and several protein domains. Starting from this information, computational methods have been used both to improve the understanding of the STAT3 functional mechanism and to design new inhibitors to be used as anticancer drugs. In this review, we will focus on the contribution of structural biology to understand the roles of STAT3, to design new inhibitors and to suggest new strategies of pharmacological intervention. Twit Text FOAVip Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development ????Int J Mol Sci http://www.kidney.de/pget.php?&tw=1&pmid=29843450 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29843450 #FOAvip English Wikipedia <ref>{{Cite pmid|29843450}}</ref> Structural Biology of STAT3 and Its Implications for Anticancer Therapies Development #MMPMID29843450 Sgrignani J; Garofalo M; Matkovic M; Merulla J; Catapano CV; Cavalli A Int J Mol Sci 2018[Jun]; 19 (6): ä PMID29843450show ga Transcription factors are proteins able to bind DNA and induce the transcription of specific genes. Consequently, they play a pivotal role in multiple cellular pathways and are frequently over-expressed or dysregulated in cancer. Here, we will focus on a specific ?signal transducer and activator of transcription? (STAT3) factor that is involved in several pathologies, including cancer. For long time, the mechanism by which STAT3 exerts its cellular functions has been summarized by a three steps process: (1) Protein phosphorylation by specific kinases, (2) dimerization promoted by phosphorylation, (3) activation of gene expression by the phosphorylated dimer. Consequently, most of the inhibitors reported in literature aimed at blocking phosphorylation and dimerization. However, recent observations reopened the debate and the entire functional mechanism has been revisited stimulating the scientific community to pursue new inhibition strategies. In particular, the dimerization of the unphosphorylated species has been experimentally demonstrated and specific roles proposed also for these dimers. Despite difficulties in the expression and purification of the full length STAT3, structural biology investigations allowed the determination of atomistic structures of STAT3 dimers and several protein domains. Starting from this information, computational methods have been used both to improve the understanding of the STAT3 functional mechanism and to design new inhibitors to be used as anticancer drugs. In this review, we will focus on the contribution of structural biology to understand the roles of STAT3, to design new inhibitors and to suggest new strategies of pharmacological intervention. äStructural Biology of STAT3 and Its Implications for Anticancer Therap(epmc).pdf DeepDyve Pubget Overpricing