FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2924408001> ?p ?o ?g. }

• W2924408001 abstract "Abstract Despite the prevalence of N-terminal acetylation (Nt-acetylation), little is known of its biological functions. In this study, we show that NatB regulates Rb mutant cell survival, EGFR/MAPK signaling activity, and EGFR signaling-dependent tumor growth. We identify Grb2/Drk, MAPK, and PP2AC as the key NatB targets of EGFR pathway. Surprisingly, NatB activity increases the levels of positive pathway components Grb2/Drk and MAPK while decreases the levels of negative pathway component PP2AC despite these proteins have the same first two amino acids that are recognized by NatB and N-end rule pathways. Mechanistically, we show that NatB regulates Grb2/Drk protein stability through its N-terminal sequences and that Grb2/Drk and MAPK are selectively degraded by the Arg/N-end rule E3 ubiquitin ligase Ubr4, which targets proteins with free N-terminus. In contrast, PP2AC is selectively degraded by the Ac/N-end rule pathway E3 ubiquitin ligase Cnot4 that targets proteins with acetylated N-terminus. These results reveal a novel mechanism by which NatB-mediated Nt-acetylation and N-end rule pathways modulate EGFR/MAPK signaling by inversely regulating the levels of positive and negative components. Since mutation or overexpression that deregulate the EGFR/Ras signaling pathway are common in human cancers and NatB subunits are significant unfavorable prognostic markers, this study can potentially lead to the development of novel therapeutic approaches. Significance Statement Nt-acetylation is often regarded as a constitutive, irreversible, and static modification that is not suited to serve regulatory functions. Our observation that Nt-acetylation by NatB coordinately regulate the levels of positive and negative components of the EGFR/MAPK pathway show that Nt-acetylation and N-end rule pathways can play important roles regulating important signaling pathways. As Acetyl-CoA level, which is influenced by cell metabolism, can be rate limiting for Nt-acetylation, our results also suggest a potentially new mechanism by which cellular metabolic status can regulate growth factor signaling." @default.
• W2924408001 created "2019-04-01" @default.
• W2924408001 creator A5042917596 @default.
• W2924408001 creator A5085722081 @default.
• W2924408001 date "2019-03-26" @default.
• W2924408001 modified "2023-09-27" @default.
• W2924408001 title "NatB modulates Rb mutant cell death and tumor growth by regulating EGFR/MAPK signaling through the N-end rule pathways" @default.
• W2924408001 cites W1553155385 @default.
• W2924408001 cites W1767581168 @default.
• W2924408001 cites W1969715546 @default.
• W2924408001 cites W1970527559 @default.
• W2924408001 cites W1988142400 @default.
• W2924408001 cites W1992418538 @default.
• W2924408001 cites W2010231891 @default.
• W2924408001 cites W2017558556 @default.
• W2924408001 cites W2018194443 @default.
• W2924408001 cites W2020478637 @default.
• W2924408001 cites W2022222857 @default.
• W2924408001 cites W2033750217 @default.
• W2924408001 cites W2039174905 @default.
• W2924408001 cites W2041330970 @default.
• W2924408001 cites W2046336727 @default.
• W2924408001 cites W2046666752 @default.
• W2924408001 cites W2047195990 @default.
• W2924408001 cites W2051683278 @default.
• W2924408001 cites W2054946171 @default.
• W2924408001 cites W2058199749 @default.
• W2924408001 cites W2065418058 @default.
• W2924408001 cites W2071028051 @default.
• W2924408001 cites W2079343812 @default.
• W2924408001 cites W2080157553 @default.
• W2924408001 cites W2081613861 @default.
• W2924408001 cites W2082702196 @default.
• W2924408001 cites W2082773871 @default.
• W2924408001 cites W2093351885 @default.
• W2924408001 cites W2101803513 @default.
• W2924408001 cites W2106876831 @default.
• W2924408001 cites W2107906416 @default.
• W2924408001 cites W2110643873 @default.
• W2924408001 cites W2113563206 @default.
• W2924408001 cites W2117520027 @default.
• W2924408001 cites W2120525124 @default.
• W2924408001 cites W2147327414 @default.
• W2924408001 cites W2156791826 @default.
• W2924408001 cites W2159006827 @default.
• W2924408001 cites W2161853394 @default.
• W2924408001 cites W2167234212 @default.
• W2924408001 cites W2169569309 @default.
• W2924408001 cites W2284990905 @default.
• W2924408001 cites W2334039989 @default.
• W2924408001 cites W2507955777 @default.
• W2924408001 cites W2604603855 @default.
• W2924408001 cites W2607257714 @default.
• W2924408001 cites W2784077309 @default.
• W2924408001 cites W2883210621 @default.
• W2924408001 doi "https://doi.org/10.1101/590349" @default.
• W2924408001 hasPublicationYear "2019" @default.
• W2924408001 type Work @default.
• W2924408001 sameAs 2924408001 @default.
• W2924408001 citedByCount "0" @default.
• W2924408001 crossrefType "posted-content" @default.
• W2924408001 hasAuthorship W2924408001A5042917596 @default.
• W2924408001 hasAuthorship W2924408001A5085722081 @default.
• W2924408001 hasBestOaLocation W29244080011 @default.
• W2924408001 hasConcept C104317684 @default.
• W2924408001 hasConcept C119157956 @default.
• W2924408001 hasConcept C134459356 @default.
• W2924408001 hasConcept C143065580 @default.
• W2924408001 hasConcept C177917778 @default.
• W2924408001 hasConcept C183786373 @default.
• W2924408001 hasConcept C185592680 @default.
• W2924408001 hasConcept C25602115 @default.
• W2924408001 hasConcept C55493867 @default.
• W2924408001 hasConcept C57074206 @default.
• W2924408001 hasConcept C62478195 @default.
• W2924408001 hasConcept C86803240 @default.
• W2924408001 hasConcept C95444343 @default.
• W2924408001 hasConceptScore W2924408001C104317684 @default.
• W2924408001 hasConceptScore W2924408001C119157956 @default.
• W2924408001 hasConceptScore W2924408001C134459356 @default.
• W2924408001 hasConceptScore W2924408001C143065580 @default.
• W2924408001 hasConceptScore W2924408001C177917778 @default.
• W2924408001 hasConceptScore W2924408001C183786373 @default.
• W2924408001 hasConceptScore W2924408001C185592680 @default.
• W2924408001 hasConceptScore W2924408001C25602115 @default.
• W2924408001 hasConceptScore W2924408001C55493867 @default.
• W2924408001 hasConceptScore W2924408001C57074206 @default.
• W2924408001 hasConceptScore W2924408001C62478195 @default.
• W2924408001 hasConceptScore W2924408001C86803240 @default.
• W2924408001 hasConceptScore W2924408001C95444343 @default.
• W2924408001 hasLocation W29244080011 @default.
• W2924408001 hasLocation W29244080012 @default.
• W2924408001 hasOpenAccess W2924408001 @default.
• W2924408001 hasPrimaryLocation W29244080011 @default.
• W2924408001 hasRelatedWork W1510940290 @default.
• W2924408001 hasRelatedWork W1967904525 @default.
• W2924408001 hasRelatedWork W2018682634 @default.
• W2924408001 hasRelatedWork W2091267676 @default.
• W2924408001 hasRelatedWork W2102368462 @default.
• W2924408001 hasRelatedWork W2766155073 @default.

• next