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10.1016/j.bbrc.2020.12.091 http://scihub22266oqcxt.onion/10.1016/j.bbrc.2020.12.091 33450483!7836930!33450483     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Biochem+Biophys+Res+Commun 2021 ; 540 (ä): 75-82 Nephropedia Template TP {{tp|p=33450483|t=2021. The papain-like protease of coronaviruses cleaves ULK1 to disrupt host autophagy |pdf=|usr=}}{{33450483}} gab.com Text The papain-like protease of coronaviruses cleaves ULK1 to disrupt host autophagy JO: Biochem Biophys Res Commun http://www.kidney.de/pget.php?&tw=1&pmid=33450483 #FOAvip The ongoing pandemic of COVID-19 alongside the outbreaks of SARS in 2003 and MERS in 2012 underscore the significance to understand betacoronaviruses as a global health challenge. SARS-CoV-2, the etiological agent for COVID-19, has infected over 50 million individuals' worldwide with more than approximately 1 million fatalities. Autophagy modulators have emerged as potential therapeutic candidates against SARS-CoV-2 but recent clinical setbacks urge for better understanding of viral subversion of autophagy. Using MHV-A59 as a model betacoronavirus, time-course infections revealed significant loss in the protein level of ULK1, a canonical autophagy-regulating kinase, and the concomitant appearance of a possible cleavage fragment. To investigate whether virus-encoded proteases target ULK1, we conducted in-vitro and cellular cleavage assays and identified ULK1 as a novel bona fide substrate of SARS-CoV-2 papain-like protease (PL(pro)). Mutagenesis studies discovered that ULK1 is cleaved at a conserved PL(pro) recognition sequence (LGGG) after G499, separating its N-terminal kinase domain from a C-terminal substrate recognition region. Over-expression of SARS-CoV-2 PL(pro) is sufficient to impair starvation-induced autophagy and disrupt formation of ULK1-ATG13 complex. Finally, we demonstrated a dual role for ULK1 in MHV-A59 replication, serving a pro-viral functions during early replication that is inactivated at late stages of infection. In conclusion, our study identified a new mechanism by which PL(pro) of betacoronaviruses induces viral pathogenesis by targeting cellular autophagy. Twit Text FOAVip The papain-like protease of coronaviruses cleaves ULK1 to disrupt host autophagy ????Biochem Biophys Res Commun http://www.kidney.de/pget.php?&tw=1&pmid=33450483 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33450483 #FOAvip English Wikipedia <ref>{{Cite pmid|33450483}}</ref> The papain-like protease of coronaviruses cleaves ULK1 to disrupt host autophagy #MMPMID33450483 Mohamud Y; Xue YC; Liu H; Ng CS; Bahreyni A; Jan E; Luo H Biochem Biophys Res Commun 2021[Feb]; 540 (ä): 75-82 PMID33450483show ga The ongoing pandemic of COVID-19 alongside the outbreaks of SARS in 2003 and MERS in 2012 underscore the significance to understand betacoronaviruses as a global health challenge. SARS-CoV-2, the etiological agent for COVID-19, has infected over 50 million individuals' worldwide with more than approximately 1 million fatalities. Autophagy modulators have emerged as potential therapeutic candidates against SARS-CoV-2 but recent clinical setbacks urge for better understanding of viral subversion of autophagy. Using MHV-A59 as a model betacoronavirus, time-course infections revealed significant loss in the protein level of ULK1, a canonical autophagy-regulating kinase, and the concomitant appearance of a possible cleavage fragment. To investigate whether virus-encoded proteases target ULK1, we conducted in-vitro and cellular cleavage assays and identified ULK1 as a novel bona fide substrate of SARS-CoV-2 papain-like protease (PL(pro)). Mutagenesis studies discovered that ULK1 is cleaved at a conserved PL(pro) recognition sequence (LGGG) after G499, separating its N-terminal kinase domain from a C-terminal substrate recognition region. Over-expression of SARS-CoV-2 PL(pro) is sufficient to impair starvation-induced autophagy and disrupt formation of ULK1-ATG13 complex. Finally, we demonstrated a dual role for ULK1 in MHV-A59 replication, serving a pro-viral functions during early replication that is inactivated at late stages of infection. In conclusion, our study identified a new mechanism by which PL(pro) of betacoronaviruses induces viral pathogenesis by targeting cellular autophagy. |*Autophagy/genetics[MESH] |Animals[MESH] |Autophagy-Related Protein-1 Homolog/genetics/*metabolism[MESH] |Cells, Cultured[MESH] |Coronavirus Papain-Like Proteases/*metabolism[MESH] |Mice[MESH]The papain-like protease of coronaviruses cleaves ULK1 to disrupt host(epmc).pdf DeepDyve Pubget Overpricing