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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       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 (PTCs) and the rapid degradation of their mRNAs by nonsense mediated RNA decay (NMD). We used virtual library screening (VLS) 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, pharmacological NMD inhibition disrupted SMG7-UPF1 interactions. When used in cells with PTC mutated p53, pharmacological 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 pharmacological NMD inhibitors can restore mRNA integrity in the presence of PTC and 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 PMID24662918show ga Many of the gene mutations found in genetic disorders, including cancer, result in premature termination codons (PTCs) and the rapid degradation of their mRNAs by nonsense mediated RNA decay (NMD). We used virtual library screening (VLS) 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, pharmacological NMD inhibition disrupted SMG7-UPF1 interactions. When used in cells with PTC mutated p53, pharmacological 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 pharmacological NMD inhibitors can restore mRNA integrity in the presence of PTC and be used as part of a strategy to restore full length protein in a variety of genetic diseases. äIdentification and characterization of small molecules that inhibit no(epmc).pdf DeepDyve Pubget Overpricing