Matches in SemOpenAlex for { <https://semopenalex.org/work/W3209600971> ?p ?o ?g. }
- W3209600971 endingPage "109953" @default.
- W3209600971 startingPage "109953" @default.
- W3209600971 abstract "Receptor clustering is the first and critical step to activate apoptosis by death receptor-5 (DR5). The recent discovery of the autoinhibitory DR5 ectodomain has challenged the long-standing view of its mechanistic activation by the natural ligand Apo2L. Because the autoinhibitory residues have remained unknown, here we characterize a crucial patch of positively charged residues (PPCR) in the highly variable domain of DR5. The PPCR electrostatically separates DR5 receptors to autoinhibit their clustering in the absence of ligand and antibody binding. Mutational substitution and antibody-mediated PPCR interference resulted in increased apoptotic cytotoxic function. A dually specific antibody that enables sustained tampering with PPCR function exceptionally enhanced DR5 clustering and apoptotic activation and distinctively improved the survival of animals bearing aggressive metastatic and recurrent tumors, whereas clinically tested DR5 antibodies without PPCR blockade function were largely ineffective. Our study provides mechanistic insights into DR5 activation and a therapeutic analytical design for potential clinical success." @default.
- W3209600971 created "2021-11-08" @default.
- W3209600971 creator A5000618994 @default.
- W3209600971 creator A5005082289 @default.
- W3209600971 creator A5005083044 @default.
- W3209600971 creator A5017177482 @default.
- W3209600971 creator A5018891733 @default.
- W3209600971 creator A5024790017 @default.
- W3209600971 creator A5028764251 @default.
- W3209600971 creator A5035746983 @default.
- W3209600971 creator A5057580188 @default.
- W3209600971 creator A5074518603 @default.
- W3209600971 date "2021-11-01" @default.
- W3209600971 modified "2023-10-14" @default.
- W3209600971 title "A patch of positively charged residues regulates the efficacy of clinical DR5 antibodies in solid tumors" @default.
- W3209600971 cites W1511853133 @default.
- W3209600971 cites W1554892411 @default.
- W3209600971 cites W1583078809 @default.
- W3209600971 cites W1911269322 @default.
- W3209600971 cites W1963083447 @default.
- W3209600971 cites W1964304371 @default.
- W3209600971 cites W1976792502 @default.
- W3209600971 cites W1991388076 @default.
- W3209600971 cites W1994251377 @default.
- W3209600971 cites W2008378153 @default.
- W3209600971 cites W2010030578 @default.
- W3209600971 cites W2016516934 @default.
- W3209600971 cites W2017086893 @default.
- W3209600971 cites W2023342930 @default.
- W3209600971 cites W2025199750 @default.
- W3209600971 cites W2039805273 @default.
- W3209600971 cites W2066962978 @default.
- W3209600971 cites W2074106785 @default.
- W3209600971 cites W2084376588 @default.
- W3209600971 cites W2085690948 @default.
- W3209600971 cites W2087590198 @default.
- W3209600971 cites W2092524729 @default.
- W3209600971 cites W2109463067 @default.
- W3209600971 cites W2111510713 @default.
- W3209600971 cites W2111823261 @default.
- W3209600971 cites W2119500275 @default.
- W3209600971 cites W2124992697 @default.
- W3209600971 cites W2169618461 @default.
- W3209600971 cites W2171653534 @default.
- W3209600971 cites W2207247751 @default.
- W3209600971 cites W2517683463 @default.
- W3209600971 cites W2606306441 @default.
- W3209600971 cites W2739863466 @default.
- W3209600971 cites W2885916464 @default.
- W3209600971 cites W2902120560 @default.
- W3209600971 cites W2919275655 @default.
- W3209600971 cites W2953553531 @default.
- W3209600971 cites W3009252026 @default.
- W3209600971 cites W304024600 @default.
- W3209600971 cites W3081836282 @default.
- W3209600971 cites W3131188136 @default.
- W3209600971 doi "https://doi.org/10.1016/j.celrep.2021.109953" @default.
- W3209600971 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34731630" @default.
- W3209600971 hasPublicationYear "2021" @default.
- W3209600971 type Work @default.
- W3209600971 sameAs 3209600971 @default.
- W3209600971 citedByCount "2" @default.
- W3209600971 countsByYear W32096009712022 @default.
- W3209600971 countsByYear W32096009712023 @default.
- W3209600971 crossrefType "journal-article" @default.
- W3209600971 hasAuthorship W3209600971A5000618994 @default.
- W3209600971 hasAuthorship W3209600971A5005082289 @default.
- W3209600971 hasAuthorship W3209600971A5005083044 @default.
- W3209600971 hasAuthorship W3209600971A5017177482 @default.
- W3209600971 hasAuthorship W3209600971A5018891733 @default.
- W3209600971 hasAuthorship W3209600971A5024790017 @default.
- W3209600971 hasAuthorship W3209600971A5028764251 @default.
- W3209600971 hasAuthorship W3209600971A5035746983 @default.
- W3209600971 hasAuthorship W3209600971A5057580188 @default.
- W3209600971 hasAuthorship W3209600971A5074518603 @default.
- W3209600971 hasBestOaLocation W32096009711 @default.
- W3209600971 hasConcept C1009742 @default.
- W3209600971 hasConcept C116569031 @default.
- W3209600971 hasConcept C14036430 @default.
- W3209600971 hasConcept C159654299 @default.
- W3209600971 hasConcept C170493617 @default.
- W3209600971 hasConcept C185592680 @default.
- W3209600971 hasConcept C190283241 @default.
- W3209600971 hasConcept C203014093 @default.
- W3209600971 hasConcept C2778468042 @default.
- W3209600971 hasConcept C502942594 @default.
- W3209600971 hasConcept C55493867 @default.
- W3209600971 hasConcept C86803240 @default.
- W3209600971 hasConcept C95444343 @default.
- W3209600971 hasConceptScore W3209600971C1009742 @default.
- W3209600971 hasConceptScore W3209600971C116569031 @default.
- W3209600971 hasConceptScore W3209600971C14036430 @default.
- W3209600971 hasConceptScore W3209600971C159654299 @default.
- W3209600971 hasConceptScore W3209600971C170493617 @default.
- W3209600971 hasConceptScore W3209600971C185592680 @default.
- W3209600971 hasConceptScore W3209600971C190283241 @default.
- W3209600971 hasConceptScore W3209600971C203014093 @default.
- W3209600971 hasConceptScore W3209600971C2778468042 @default.