FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002302593> ?p ?o ?g. }

• W2002302593 endingPage "12312" @default.
• W2002302593 startingPage "12305" @default.
• W2002302593 abstract "HA22 is a recombinant immunotoxin that kills CD22-expressing cells by ADP-ribosylating and inactivating elongation factor-2 (EF2). HA22 is composed of an Fv that binds to CD22 fused to a portion of Pseudomonas exotoxin A. HA22 is very active in drug-resistant hairy cell leukemia but is less active in children with acute lymphoblastic leukemia. To understand why some patients do not respond to HA22, we isolated an HA22-resistant lymphoma cell line and showed that resistance was due to the inability of HA22 to ADP-ribosylate and inactivate EF2. We analyzed the diphthamide synthesis genes and found that the WDR85 gene was deleted. We show that WDR85 knockdown conferred HA22 resistance to sensitive cells and that sensitivity was restored by introduction of a WDR85 cDNA into resistant cells. Analysis of EF2 in the mutant cells revealed a novel form of diphthamide with an additional methyl group that prevented ADP-ribosylation and inactivation of EF2. The abnormal methylation appeared to be catalyzed by DPH5. Inactivation of the WDR85 gene could be a mechanism of immunotoxin resistance in patients undergoing immunotoxin therapy. HA22 is a recombinant immunotoxin that kills CD22-expressing cells by ADP-ribosylating and inactivating elongation factor-2 (EF2). HA22 is composed of an Fv that binds to CD22 fused to a portion of Pseudomonas exotoxin A. HA22 is very active in drug-resistant hairy cell leukemia but is less active in children with acute lymphoblastic leukemia. To understand why some patients do not respond to HA22, we isolated an HA22-resistant lymphoma cell line and showed that resistance was due to the inability of HA22 to ADP-ribosylate and inactivate EF2. We analyzed the diphthamide synthesis genes and found that the WDR85 gene was deleted. We show that WDR85 knockdown conferred HA22 resistance to sensitive cells and that sensitivity was restored by introduction of a WDR85 cDNA into resistant cells. Analysis of EF2 in the mutant cells revealed a novel form of diphthamide with an additional methyl group that prevented ADP-ribosylation and inactivation of EF2. The abnormal methylation appeared to be catalyzed by DPH5. Inactivation of the WDR85 gene could be a mechanism of immunotoxin resistance in patients undergoing immunotoxin therapy." @default.
• W2002302593 created "2016-06-24" @default.
• W2002302593 creator A5002518199 @default.
• W2002302593 creator A5002583441 @default.
• W2002302593 creator A5048276478 @default.
• W2002302593 creator A5056573254 @default.
• W2002302593 creator A5060090685 @default.
• W2002302593 creator A5076554157 @default.
• W2002302593 creator A5083416957 @default.
• W2002302593 date "2013-04-01" @default.
• W2002302593 modified "2023-10-04" @default.
• W2002302593 title "A Modified Form of Diphthamide Causes Immunotoxin Resistance in a Lymphoma Cell Line with a Deletion of the WDR85 Gene" @default.
• W2002302593 cites W1498019036 @default.
• W2002302593 cites W1533548496 @default.
• W2002302593 cites W1599883596 @default.
• W2002302593 cites W1980908431 @default.
• W2002302593 cites W1993866387 @default.
• W2002302593 cites W2003787610 @default.
• W2002302593 cites W2012598468 @default.
• W2002302593 cites W2014283692 @default.
• W2002302593 cites W2015758016 @default.
• W2002302593 cites W2023075166 @default.
• W2002302593 cites W2023910429 @default.
• W2002302593 cites W2033870792 @default.
• W2002302593 cites W2045117614 @default.
• W2002302593 cites W2074162426 @default.
• W2002302593 cites W2076558529 @default.
• W2002302593 cites W2091778695 @default.
• W2002302593 cites W2093569530 @default.
• W2002302593 cites W2120104555 @default.
• W2002302593 cites W2126333883 @default.
• W2002302593 cites W2127530853 @default.
• W2002302593 cites W2128119454 @default.
• W2002302593 cites W2132059723 @default.
• W2002302593 cites W2133413107 @default.
• W2002302593 cites W2147418863 @default.
• W2002302593 cites W2156671071 @default.
• W2002302593 cites W2158769513 @default.
• W2002302593 cites W2592851172 @default.
• W2002302593 doi "https://doi.org/10.1074/jbc.m113.461343" @default.
• W2002302593 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3636914" @default.
• W2002302593 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23486472" @default.
• W2002302593 hasPublicationYear "2013" @default.
• W2002302593 type Work @default.
• W2002302593 sameAs 2002302593 @default.
• W2002302593 citedByCount "27" @default.
• W2002302593 countsByYear W20023025932013 @default.
• W2002302593 countsByYear W20023025932014 @default.
• W2002302593 countsByYear W20023025932015 @default.
• W2002302593 countsByYear W20023025932016 @default.
• W2002302593 countsByYear W20023025932017 @default.
• W2002302593 countsByYear W20023025932018 @default.
• W2002302593 countsByYear W20023025932019 @default.
• W2002302593 countsByYear W20023025932020 @default.
• W2002302593 countsByYear W20023025932022 @default.
• W2002302593 crossrefType "journal-article" @default.
• W2002302593 hasAuthorship W2002302593A5002518199 @default.
• W2002302593 hasAuthorship W2002302593A5002583441 @default.
• W2002302593 hasAuthorship W2002302593A5048276478 @default.
• W2002302593 hasAuthorship W2002302593A5056573254 @default.
• W2002302593 hasAuthorship W2002302593A5060090685 @default.
• W2002302593 hasAuthorship W2002302593A5076554157 @default.
• W2002302593 hasAuthorship W2002302593A5083416957 @default.
• W2002302593 hasBestOaLocation W20023025931 @default.
• W2002302593 hasConcept C104317684 @default.
• W2002302593 hasConcept C109316439 @default.
• W2002302593 hasConcept C115085202 @default.
• W2002302593 hasConcept C153911025 @default.
• W2002302593 hasConcept C182179738 @default.
• W2002302593 hasConcept C202751555 @default.
• W2002302593 hasConcept C2777367657 @default.
• W2002302593 hasConcept C2778461978 @default.
• W2002302593 hasConcept C2778723905 @default.
• W2002302593 hasConcept C40767141 @default.
• W2002302593 hasConcept C502942594 @default.
• W2002302593 hasConcept C54355233 @default.
• W2002302593 hasConcept C55493867 @default.
• W2002302593 hasConcept C81885089 @default.
• W2002302593 hasConcept C86803240 @default.
• W2002302593 hasConcept C89423630 @default.
• W2002302593 hasConceptScore W2002302593C104317684 @default.
• W2002302593 hasConceptScore W2002302593C109316439 @default.
• W2002302593 hasConceptScore W2002302593C115085202 @default.
• W2002302593 hasConceptScore W2002302593C153911025 @default.
• W2002302593 hasConceptScore W2002302593C182179738 @default.
• W2002302593 hasConceptScore W2002302593C202751555 @default.
• W2002302593 hasConceptScore W2002302593C2777367657 @default.
• W2002302593 hasConceptScore W2002302593C2778461978 @default.
• W2002302593 hasConceptScore W2002302593C2778723905 @default.
• W2002302593 hasConceptScore W2002302593C40767141 @default.
• W2002302593 hasConceptScore W2002302593C502942594 @default.
• W2002302593 hasConceptScore W2002302593C54355233 @default.
• W2002302593 hasConceptScore W2002302593C55493867 @default.
• W2002302593 hasConceptScore W2002302593C81885089 @default.
• W2002302593 hasConceptScore W2002302593C86803240 @default.
• W2002302593 hasConceptScore W2002302593C89423630 @default.
• W2002302593 hasIssue "17" @default.
• W2002302593 hasLocation W20023025931 @default.

• next