Matches in SemOpenAlex for { <https://semopenalex.org/work/W4300688074> ?p ?o ?g. }
- W4300688074 endingPage "1856" @default.
- W4300688074 startingPage "1846" @default.
- W4300688074 abstract "Abstract Tumor protein p63 (TP63) is a member of the TP53 protein family that are important for development and in tumor suppression. Unlike TP53, TP63 is rarely mutated in cancer, but instead different TP63 isoforms regulate its activity. TA isoforms (TAp63) act as tumor suppressors, whereas ΔN isoforms are strong drivers of squamous or squamous-like cancers. Many of these tumors become addicted to ΔN isoforms and removal of ΔN isoforms result in cancer cell death. Furthermore, some TP53 conformational mutants (TP53CM) gain the ability to interact with TAp63 isoforms and inhibit their antitumorigenic function, while indirectly promoting tumorigenic function of ΔN isoforms, but the exact mechanism of TP63–TP53CM interaction is unclear. The changes in the balance of TP63 isoform activity are crucial to understanding the transition between normal and tumor cells. Here, we modeled TP63–TP53CM complex using computational approaches. We then used our models to design peptides to disrupt the TP63–TP53CM interaction and restore antitumorigenic TAp63 function. In addition, we studied ΔN isoform oligomerization and designed peptides to inhibit its oligomerization and reduce their tumorigenic activity. We show that some of our peptides promoted cell death in a TP63 highly expressed cancer cell line, but not in a TP63 lowly expressed cancer cell line. Furthermore, we performed kinetic–binding assays to validate binding of our peptides to their targets. Our computational and experimental analyses present a detailed model for the TP63–TP53CM interaction and provide a framework for potential therapeutic peptides for the elimination of TP53CM cancer cells." @default.
- W4300688074 created "2022-10-04" @default.
- W4300688074 creator A5004136114 @default.
- W4300688074 creator A5058286112 @default.
- W4300688074 creator A5084145479 @default.
- W4300688074 date "2022-10-03" @default.
- W4300688074 modified "2023-10-18" @default.
- W4300688074 title "Computational Modeling of TP63–TP53 Interaction and Rational Design of Inhibitors: Implications for Therapeutics" @default.
- W4300688074 cites W1534987406 @default.
- W4300688074 cites W1584759442 @default.
- W4300688074 cites W1640635403 @default.
- W4300688074 cites W1982196959 @default.
- W4300688074 cites W1984247920 @default.
- W4300688074 cites W1987134040 @default.
- W4300688074 cites W1990508187 @default.
- W4300688074 cites W2010076108 @default.
- W4300688074 cites W2014938226 @default.
- W4300688074 cites W2028586759 @default.
- W4300688074 cites W2042316019 @default.
- W4300688074 cites W2048168721 @default.
- W4300688074 cites W2057477511 @default.
- W4300688074 cites W2070206037 @default.
- W4300688074 cites W2078692783 @default.
- W4300688074 cites W2081693079 @default.
- W4300688074 cites W2083467502 @default.
- W4300688074 cites W2087574732 @default.
- W4300688074 cites W2088744498 @default.
- W4300688074 cites W2091084179 @default.
- W4300688074 cites W2092073124 @default.
- W4300688074 cites W2094366504 @default.
- W4300688074 cites W2115860567 @default.
- W4300688074 cites W2117541321 @default.
- W4300688074 cites W2142839601 @default.
- W4300688074 cites W2154019529 @default.
- W4300688074 cites W2155030096 @default.
- W4300688074 cites W2161605421 @default.
- W4300688074 cites W2166476348 @default.
- W4300688074 cites W2167398093 @default.
- W4300688074 cites W2285093314 @default.
- W4300688074 cites W2306983684 @default.
- W4300688074 cites W2415639371 @default.
- W4300688074 cites W2506760085 @default.
- W4300688074 cites W2739354616 @default.
- W4300688074 cites W2763474643 @default.
- W4300688074 cites W2901608487 @default.
- W4300688074 cites W2903777166 @default.
- W4300688074 cites W2908811118 @default.
- W4300688074 cites W2936514784 @default.
- W4300688074 cites W2994288809 @default.
- W4300688074 cites W3013763244 @default.
- W4300688074 cites W3020400196 @default.
- W4300688074 cites W3113741077 @default.
- W4300688074 cites W3128581905 @default.
- W4300688074 cites W3206567829 @default.
- W4300688074 doi "https://doi.org/10.1158/1535-7163.mct-22-0008" @default.
- W4300688074 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36190964" @default.
- W4300688074 hasPublicationYear "2022" @default.
- W4300688074 type Work @default.
- W4300688074 citedByCount "1" @default.
- W4300688074 countsByYear W43006880742023 @default.
- W4300688074 crossrefType "journal-article" @default.
- W4300688074 hasAuthorship W4300688074A5004136114 @default.
- W4300688074 hasAuthorship W4300688074A5058286112 @default.
- W4300688074 hasAuthorship W4300688074A5084145479 @default.
- W4300688074 hasBestOaLocation W43006880741 @default.
- W4300688074 hasConcept C104317684 @default.
- W4300688074 hasConcept C121608353 @default.
- W4300688074 hasConcept C14036430 @default.
- W4300688074 hasConcept C143065580 @default.
- W4300688074 hasConcept C179185449 @default.
- W4300688074 hasConcept C185592680 @default.
- W4300688074 hasConcept C502942594 @default.
- W4300688074 hasConcept C53105671 @default.
- W4300688074 hasConcept C53345823 @default.
- W4300688074 hasConcept C54355233 @default.
- W4300688074 hasConcept C55493867 @default.
- W4300688074 hasConcept C86803240 @default.
- W4300688074 hasConcept C95444343 @default.
- W4300688074 hasConcept C96232424 @default.
- W4300688074 hasConceptScore W4300688074C104317684 @default.
- W4300688074 hasConceptScore W4300688074C121608353 @default.
- W4300688074 hasConceptScore W4300688074C14036430 @default.
- W4300688074 hasConceptScore W4300688074C143065580 @default.
- W4300688074 hasConceptScore W4300688074C179185449 @default.
- W4300688074 hasConceptScore W4300688074C185592680 @default.
- W4300688074 hasConceptScore W4300688074C502942594 @default.
- W4300688074 hasConceptScore W4300688074C53105671 @default.
- W4300688074 hasConceptScore W4300688074C53345823 @default.
- W4300688074 hasConceptScore W4300688074C54355233 @default.
- W4300688074 hasConceptScore W4300688074C55493867 @default.
- W4300688074 hasConceptScore W4300688074C86803240 @default.
- W4300688074 hasConceptScore W4300688074C95444343 @default.
- W4300688074 hasConceptScore W4300688074C96232424 @default.
- W4300688074 hasFunder F4320334223 @default.
- W4300688074 hasIssue "12" @default.
- W4300688074 hasLocation W43006880741 @default.
- W4300688074 hasLocation W43006880742 @default.
- W4300688074 hasOpenAccess W4300688074 @default.