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10.1158/0008-5472.CAN-13-2235 http://scihub22266oqcxt.onion/10.1158/0008-5472.CAN-13-2235 C4040335!4040335 !24662918     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 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\24662918 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Cancer+Res 2014 ; 74 (11 ): 3104-13 Nephropedia Template TP {{tp|p=24662918 |t=2014. Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations |pdf=|usr=}}{{24662918 }} gab.com Text Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations JO: Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=24662918 #FOAvip Many of the gene mutations found in genetic disorders, including cancer, result in premature termination codons (PTC) and the rapid degradation of their mRNAs by nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a pocket in the SMG7 protein, a key component of the NMD mechanism, to identify compounds that disrupt the SMG7-UPF1 complex and inhibit NMD. Several of these compounds upregulated NMD-targeted mRNAs at nanomolar concentrations, with minimal toxicity in cell-based assays. As expected, pharmacologic NMD inhibition disrupted SMG7-UPF1 interactions. When used in cells with PTC-mutated p53, pharmacologic NMD inhibition combined with a PTC "read-through" drug led to restoration of full-length p53 protein, upregulation of p53 downstream transcripts, and cell death. These studies serve as proof-of-concept that pharmacologic NMD inhibitors can restore mRNA integrity in the presence of PTC and can be used as part of a strategy to restore full-length protein in a variety of genetic diseases. Twit Text FOAVip Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations ????Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=24662918 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24662918 #FOAvip English Wikipedia <ref>{{Cite pmid|24662918 }}</ref> Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations #MMPMID24662918 Martin L ; Grigoryan A ; Wang D ; Wang J ; Breda L ; Rivella S ; Cardozo T ; Gardner LB Cancer Res 2014[Jun]; 74 (11 ): 3104-13 PMID24662918 show ga Many of the gene mutations found in genetic disorders, including cancer, result in premature termination codons (PTC) and the rapid degradation of their mRNAs by nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a pocket in the SMG7 protein, a key component of the NMD mechanism, to identify compounds that disrupt the SMG7-UPF1 complex and inhibit NMD. Several of these compounds upregulated NMD-targeted mRNAs at nanomolar concentrations, with minimal toxicity in cell-based assays. As expected, pharmacologic NMD inhibition disrupted SMG7-UPF1 interactions. When used in cells with PTC-mutated p53, pharmacologic NMD inhibition combined with a PTC "read-through" drug led to restoration of full-length p53 protein, upregulation of p53 downstream transcripts, and cell death. These studies serve as proof-of-concept that pharmacologic NMD inhibitors can restore mRNA integrity in the presence of PTC and can be used as part of a strategy to restore full-length protein in a variety of genetic diseases. |*Codon, Nonsense [MESH] |Carrier Proteins/genetics [MESH] |Cell Death/drug effects/genetics [MESH] |Cell Line [MESH] |Cell Line, Tumor [MESH] |HCT116 Cells [MESH] |HEK293 Cells [MESH] |HeLa Cells [MESH] |Humans [MESH] |Nonsense Mediated mRNA Decay/*drug effects/genetics [MESH] |RNA Helicases [MESH] |RNA, Messenger/genetics [MESH] |Small Molecule Libraries/*pharmacology [MESH] |Trans-Activators/genetics [MESH] |Tumor Suppressor Protein p53/*genetics [MESH]Identification and characterization of small molecules that inhibit (epmc).pdf DeepDyve Pubget Overpricing