FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896574543> ?p ?o ?g. }

• W2896574543 endingPage "e0206014" @default.
• W2896574543 startingPage "e0206014" @default.
• W2896574543 abstract "Mutations at position K171 in the kinase activation loop of Inhibitor of κB kinase beta (IKKβ) occur in multiple myeloma, spleen marginal zone lymphoma and mantle cell lymphoma. Previously, we demonstrated that these result in constitutive kinase activation and stimulate Signal Transducer and Activator of Transcription 3 (STAT3). This work also identified K147 as a site of K63-linked regulatory ubiquitination required for activation of signaling pathways. We now present a more detailed analysis of ubiquitination sites together with a comprehensive examination of the signaling pathways activated by IKKβ K171E mutants. Downstream activation of STAT3 is dependent upon the activity of: UBE2N, the E2 ubiquitin ligase involved in K63-linked ubiquitination; TAK1 (MAP3K7), or TGFβ Activated Kinase, which forms a complex required for NFκB activation; JAK kinases, involved proximally in the phosphorylation of STAT transcription factors in response to inflammatory cytokines; and gp130, or IL-6 Receptor Subunit Beta which, upon binding IL-6 or other specific cytokines, undergoes homodimerization leading to activation of associated JAKs, resulting in STAT activation. We further demonstrate, using an IL-6-responsive cell line, that IKKβ K171E mutants stimulate the release of IL-6 activity into conditioned media. These results show that IKKβ K171E mutants trigger an autocrine loop in which IL-6 is secreted and binds to the IL-6 receptor complex gp130, resulting in JAK activation. Lastly, by examining the differential abundance of proteins associated with K63-only-ubiquitinated IKKβ K171E, proteomic analysis demonstrates the global activation of proliferative responses. As cancers harboring K171-mutated IKKβ are likely to also exhibit activated STAT3 and p44/42 MAPK (Erk1/2), this suggests the possibility of using MAPK (Erk1/2) and JAK inhibitors, or specific ubiquitination inhibitors. K63-linked ubiquitination occurs in other kinases at sites homologous to K147 in IKKβ, including K578 in BRAF V600E, which serves as an oncogenic driver in melanoma and other cancers." @default.
• W2896574543 created "2018-10-26" @default.
• W2896574543 creator A5010667811 @default.
• W2896574543 creator A5017942275 @default.
• W2896574543 creator A5037352219 @default.
• W2896574543 creator A5052331149 @default.
• W2896574543 creator A5055559585 @default.
• W2896574543 creator A5057457409 @default.
• W2896574543 creator A5060342014 @default.
• W2896574543 creator A5087049810 @default.
• W2896574543 creator A5088645808 @default.
• W2896574543 date "2018-10-18" @default.
• W2896574543 modified "2023-09-26" @default.
• W2896574543 title "Oncogenic mutations in IKKβ function through global changes induced by K63-linked ubiquitination and result in autocrine stimulation" @default.
• W2896574543 cites W1542395305 @default.
• W2896574543 cites W1854727002 @default.
• W2896574543 cites W1887283207 @default.
• W2896574543 cites W1894198394 @default.
• W2896574543 cites W1980548655 @default.
• W2896574543 cites W1985821753 @default.
• W2896574543 cites W1986906983 @default.
• W2896574543 cites W2000387935 @default.
• W2896574543 cites W2013178046 @default.
• W2896574543 cites W2015341962 @default.
• W2896574543 cites W2016603053 @default.
• W2896574543 cites W2024040061 @default.
• W2896574543 cites W2025884466 @default.
• W2896574543 cites W2028544780 @default.
• W2896574543 cites W2038331455 @default.
• W2896574543 cites W2043652375 @default.
• W2896574543 cites W2044368898 @default.
• W2896574543 cites W2044759030 @default.
• W2896574543 cites W2045305556 @default.
• W2896574543 cites W2050723350 @default.
• W2896574543 cites W2053372168 @default.
• W2896574543 cites W2068547646 @default.
• W2896574543 cites W2071659155 @default.
• W2896574543 cites W2077945837 @default.
• W2896574543 cites W2078680591 @default.
• W2896574543 cites W2093396272 @default.
• W2896574543 cites W2096153562 @default.
• W2896574543 cites W2100051175 @default.
• W2896574543 cites W2101035019 @default.
• W2896574543 cites W2107282910 @default.
• W2896574543 cites W2116628300 @default.
• W2896574543 cites W2123106337 @default.
• W2896574543 cites W2128800470 @default.
• W2896574543 cites W2130410032 @default.
• W2896574543 cites W2141032550 @default.
• W2896574543 cites W2163966171 @default.
• W2896574543 cites W2167844024 @default.
• W2896574543 cites W2170776626 @default.
• W2896574543 cites W2175693901 @default.
• W2896574543 cites W2330912841 @default.
• W2896574543 cites W2463195069 @default.
• W2896574543 cites W2478314490 @default.
• W2896574543 cites W2510050480 @default.
• W2896574543 cites W2611696724 @default.
• W2896574543 cites W2785201697 @default.
• W2896574543 doi "https://doi.org/10.1371/journal.pone.0206014" @default.
• W2896574543 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6193727" @default.
• W2896574543 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30335863" @default.
• W2896574543 hasPublicationYear "2018" @default.
• W2896574543 type Work @default.
• W2896574543 sameAs 2896574543 @default.
• W2896574543 citedByCount "3" @default.
• W2896574543 countsByYear W28965745432021 @default.
• W2896574543 countsByYear W28965745432022 @default.
• W2896574543 crossrefType "journal-article" @default.
• W2896574543 hasAuthorship W2896574543A5010667811 @default.
• W2896574543 hasAuthorship W2896574543A5017942275 @default.
• W2896574543 hasAuthorship W2896574543A5037352219 @default.
• W2896574543 hasAuthorship W2896574543A5052331149 @default.
• W2896574543 hasAuthorship W2896574543A5055559585 @default.
• W2896574543 hasAuthorship W2896574543A5057457409 @default.
• W2896574543 hasAuthorship W2896574543A5060342014 @default.
• W2896574543 hasAuthorship W2896574543A5087049810 @default.
• W2896574543 hasAuthorship W2896574543A5088645808 @default.
• W2896574543 hasBestOaLocation W28965745431 @default.
• W2896574543 hasConcept C100175707 @default.
• W2896574543 hasConcept C104317684 @default.
• W2896574543 hasConcept C112392421 @default.
• W2896574543 hasConcept C11960822 @default.
• W2896574543 hasConcept C126037660 @default.
• W2896574543 hasConcept C128240485 @default.
• W2896574543 hasConcept C134459356 @default.
• W2896574543 hasConcept C170493617 @default.
• W2896574543 hasConcept C184235292 @default.
• W2896574543 hasConcept C25602115 @default.
• W2896574543 hasConcept C2777730290 @default.
• W2896574543 hasConcept C2778923194 @default.
• W2896574543 hasConcept C32465701 @default.
• W2896574543 hasConcept C502942594 @default.
• W2896574543 hasConcept C55493867 @default.
• W2896574543 hasConcept C62478195 @default.
• W2896574543 hasConcept C86803240 @default.
• W2896574543 hasConcept C95444343 @default.
• W2896574543 hasConceptScore W2896574543C100175707 @default.

• next