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10.1038/leu.2017.334 http://scihub22266oqcxt.onion/10.1038/leu.2017.334 C5871539!5871539 !29158558     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29158558 &cmd=llinks): Failed to open stream: HTTP request failed! 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Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma |pdf=|usr=}}{{29158558 }} gab.com Text Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma JO: Leukemia http://www.kidney.de/pget.php?&tw=1&pmid=29158558 #FOAvip Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-?B signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-?B inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome. Twit Text FOAVip Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma ????Leukemia http://www.kidney.de/pget.php?&tw=1&pmid=29158558 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29158558 #FOAvip English Wikipedia <ref>{{Cite pmid|29158558 }}</ref> Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma #MMPMID29158558 Gullà A ; Hideshima T ; Bianchi G ; Fulciniti M ; Kemal Samur M ; Qi J ; Tai YT ; Harada T ; Morelli E ; Amodio N ; Carrasco R ; Tagliaferri P ; Munshi NC ; Tassone P ; Anderson KC Leukemia 2018[Apr]; 32 (4 ): 996-1002 PMID29158558 show ga Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-?B signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-?B inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome. |Animals [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/drug effects/physiology [MESH] |Humans [MESH] |Isoquinolines/pharmacology [MESH] |Multiple Myeloma/*metabolism/*pathology [MESH] |NF-kappa B/metabolism [MESH] |Prognosis [MESH] |Protein-Arginine N-Methyltransferases/*metabolism [MESH] |Pyrimidines/pharmacology [MESH] |Ribonucleoproteins/metabolism [MESH]Protein arginine methyltransferase 5 has prognostic relevance and is a(epmc).pdf DeepDyve Pubget Overpricing