FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3016574836> ?p ?o ?g. }

• W3016574836 endingPage "7441" @default.
• W3016574836 startingPage "7431" @default.
• W3016574836 abstract "Lytic replication of Epstein-Barr virus (EBV) is not only essential for its cell–to–cell spread and host–to–host transmission, but it also contributes to EBV-induced oncogenesis. Thus, blocking EBV lytic replication could be a strategy for managing EBV-associated diseases. Previously, we identified a series of natural lignans isolated from the roots of Saururus chinensis (Asian lizard's tail) that efficiently block EBV lytic replication and virion production with low cytotoxicity. In this study, we attempted to elucidate the molecular mechanism by which these lignans inhibit EBV lytic replication. We found that a representative compound, CSC27 (manassantin B), inhibits EBV lytic replication by suppressing the expression of EBV immediate-early gene BZLF1 via disruption of AP-1 signal transduction. Further analysis revealed that manassantin B specifically blocks the mammalian target of rapamycin complex 2 (mTORC2)-mediated phosphorylation of AKT Ser/Thr protein kinase at Ser-473 and protein kinase Cα (PKCα) at Ser-657. Using phosphoinositide 3-kinase–AKT-specific inhibitors for kinase mapping and shRNA-mediated gene silencing, we validated that manassantin B abrogates EBV lytic replication by inhibiting mTORC2 activity and thereby blocking the mTORC2–PKC/AKT-signaling pathway. These results suggest that mTORC2 may have utility as an antiviral drug target against EBV infections and also reveal that manassantin B has potential therapeutic value for managing cancers that depend on mTORC2 signaling for survival. Lytic replication of Epstein-Barr virus (EBV) is not only essential for its cell–to–cell spread and host–to–host transmission, but it also contributes to EBV-induced oncogenesis. Thus, blocking EBV lytic replication could be a strategy for managing EBV-associated diseases. Previously, we identified a series of natural lignans isolated from the roots of Saururus chinensis (Asian lizard's tail) that efficiently block EBV lytic replication and virion production with low cytotoxicity. In this study, we attempted to elucidate the molecular mechanism by which these lignans inhibit EBV lytic replication. We found that a representative compound, CSC27 (manassantin B), inhibits EBV lytic replication by suppressing the expression of EBV immediate-early gene BZLF1 via disruption of AP-1 signal transduction. Further analysis revealed that manassantin B specifically blocks the mammalian target of rapamycin complex 2 (mTORC2)-mediated phosphorylation of AKT Ser/Thr protein kinase at Ser-473 and protein kinase Cα (PKCα) at Ser-657. Using phosphoinositide 3-kinase–AKT-specific inhibitors for kinase mapping and shRNA-mediated gene silencing, we validated that manassantin B abrogates EBV lytic replication by inhibiting mTORC2 activity and thereby blocking the mTORC2–PKC/AKT-signaling pathway. These results suggest that mTORC2 may have utility as an antiviral drug target against EBV infections and also reveal that manassantin B has potential therapeutic value for managing cancers that depend on mTORC2 signaling for survival." @default.
• W3016574836 created "2020-04-24" @default.
• W3016574836 creator A5003642180 @default.
• W3016574836 creator A5025878893 @default.
• W3016574836 creator A5038906848 @default.
• W3016574836 creator A5041437951 @default.
• W3016574836 creator A5046225712 @default.
• W3016574836 creator A5064696395 @default.
• W3016574836 creator A5068482144 @default.
• W3016574836 creator A5070005587 @default.
• W3016574836 date "2020-05-01" @default.
• W3016574836 modified "2023-10-17" @default.
• W3016574836 title "The mTOR inhibitor manassantin B reveals a crucial role of mTORC2 signaling in Epstein-Barr virus reactivation" @default.
• W3016574836 cites W1525526263 @default.
• W3016574836 cites W1578954095 @default.
• W3016574836 cites W1652755023 @default.
• W3016574836 cites W1743579359 @default.
• W3016574836 cites W1760923416 @default.
• W3016574836 cites W1838401124 @default.
• W3016574836 cites W1968017437 @default.
• W3016574836 cites W1976008877 @default.
• W3016574836 cites W1977809195 @default.
• W3016574836 cites W1978481580 @default.
• W3016574836 cites W1979169579 @default.
• W3016574836 cites W1986301677 @default.
• W3016574836 cites W1992198197 @default.
• W3016574836 cites W1992696389 @default.
• W3016574836 cites W1993753373 @default.
• W3016574836 cites W1994898506 @default.
• W3016574836 cites W1999211774 @default.
• W3016574836 cites W2006559495 @default.
• W3016574836 cites W2014006738 @default.
• W3016574836 cites W2024508390 @default.
• W3016574836 cites W2029542200 @default.
• W3016574836 cites W2039628288 @default.
• W3016574836 cites W2047392226 @default.
• W3016574836 cites W2054654563 @default.
• W3016574836 cites W2055892558 @default.
• W3016574836 cites W2060905299 @default.
• W3016574836 cites W2062307277 @default.
• W3016574836 cites W2065887259 @default.
• W3016574836 cites W2073631928 @default.
• W3016574836 cites W2077820455 @default.
• W3016574836 cites W2086484834 @default.
• W3016574836 cites W2092626295 @default.
• W3016574836 cites W2100870126 @default.
• W3016574836 cites W2112296880 @default.
• W3016574836 cites W2118897660 @default.
• W3016574836 cites W2123029438 @default.
• W3016574836 cites W2124147502 @default.
• W3016574836 cites W2131153411 @default.
• W3016574836 cites W2138044466 @default.
• W3016574836 cites W2139713301 @default.
• W3016574836 cites W2146779691 @default.
• W3016574836 cites W2152289580 @default.
• W3016574836 cites W2317192801 @default.
• W3016574836 cites W2336900894 @default.
• W3016574836 cites W2388163742 @default.
• W3016574836 cites W2593816418 @default.
• W3016574836 cites W2617832733 @default.
• W3016574836 cites W2776867289 @default.
• W3016574836 cites W2811106767 @default.
• W3016574836 cites W3149827507 @default.
• W3016574836 cites W4238567307 @default.
• W3016574836 cites W4375267536 @default.
• W3016574836 doi "https://doi.org/10.1074/jbc.ra120.012645" @default.
• W3016574836 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7247311" @default.
• W3016574836 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33516362" @default.
• W3016574836 hasPublicationYear "2020" @default.
• W3016574836 type Work @default.
• W3016574836 sameAs 3016574836 @default.
• W3016574836 citedByCount "10" @default.
• W3016574836 countsByYear W30165748362020 @default.
• W3016574836 countsByYear W30165748362021 @default.
• W3016574836 countsByYear W30165748362022 @default.
• W3016574836 countsByYear W30165748362023 @default.
• W3016574836 crossrefType "journal-article" @default.
• W3016574836 hasAuthorship W3016574836A5003642180 @default.
• W3016574836 hasAuthorship W3016574836A5025878893 @default.
• W3016574836 hasAuthorship W3016574836A5038906848 @default.
• W3016574836 hasAuthorship W3016574836A5041437951 @default.
• W3016574836 hasAuthorship W3016574836A5046225712 @default.
• W3016574836 hasAuthorship W3016574836A5064696395 @default.
• W3016574836 hasAuthorship W3016574836A5068482144 @default.
• W3016574836 hasAuthorship W3016574836A5070005587 @default.
• W3016574836 hasBestOaLocation W30165748361 @default.
• W3016574836 hasConcept C104317684 @default.
• W3016574836 hasConcept C107846503 @default.
• W3016574836 hasConcept C119056186 @default.
• W3016574836 hasConcept C140704245 @default.
• W3016574836 hasConcept C159047783 @default.
• W3016574836 hasConcept C182615771 @default.
• W3016574836 hasConcept C2522874641 @default.
• W3016574836 hasConcept C2776409557 @default.
• W3016574836 hasConcept C2780727368 @default.
• W3016574836 hasConcept C2781295983 @default.
• W3016574836 hasConcept C2781375147 @default.
• W3016574836 hasConcept C502942594 @default.

• next