FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2892087897> ?p ?o ?g. }

• W2892087897 abstract "Ponatinib is a multi-targeted third generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia (CML) patients harboring the Abelson (Abl)-breakpoint cluster region (Bcr) T315I mutation. In spite of having superb clinical efficacy, ponatinib triggers severe vascular adverse events (VAEs) that significantly limit its therapeutic potential. On vascular endothelial cells (ECs), ponatinib promotes EC dysfunction and apoptosis, and inhibits angiogenesis. Furthermore, ponatinib-mediated anti-angiogenic effect has been suggested to play a partial role in systemic and pulmonary hypertension via inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Even though ponatinib-associated VAEs are well documented, their etiology remains largely unknown, making it difficult to efficiently counteract treatment-related adversities. Therefore, a better understanding of the mechanisms by which ponatinib mediates VAEs is critical. In cultured human aortic ECs (HAECs) treated with ponatinib, we found an increase in nuclear factor NF-kB/p65 phosphorylation and NF-kB activity, inflammatory gene expression, cell permeability, and cell apoptosis. Mechanistically, ponatinib abolished extracellular signal-regulated kinase 5 (ERK5) transcriptional activity even under activation by its upstream kinase mitogen-activated protein kinase kinase 5α (CA-MEK5α). Ponatinib also diminished expression of ERK5 responsive genes such as Krüppel-like Factor 2/4 (klf2/4) and eNOS. Because ERK5 SUMOylation counteracts its transcriptional activity, we examined the effect of ponatinib on ERK5 SUMOylation, and found that ERK5 SUMOylation is increased by ponatinib. We also found that ponatibib-mediated increased inflammatory gene expression and decreased anti-inflammatory gene expression were reversed when ERK5 SUMOylation was inhibited endogenously or exogenously. Overall, we propose a novel mechanism by which ponatinib up-regulates endothelial ERK5 SUMOylation and shifts ECs to an inflammatory phenotype, disrupting vascular homeostasis." @default.
• W2892087897 created "2018-09-27" @default.
• W2892087897 creator A5000786208 @default.
• W2892087897 creator A5003052748 @default.
• W2892087897 creator A5019846091 @default.
• W2892087897 creator A5030073630 @default.
• W2892087897 creator A5030632051 @default.
• W2892087897 creator A5040474378 @default.
• W2892087897 creator A5041828251 @default.
• W2892087897 creator A5045923653 @default.
• W2892087897 creator A5090963093 @default.
• W2892087897 date "2018-09-06" @default.
• W2892087897 modified "2023-10-12" @default.
• W2892087897 title "Ponatinib Activates an Inflammatory Response in Endothelial Cells via ERK5 SUMOylation" @default.
• W2892087897 cites W1601066507 @default.
• W2892087897 cites W1627448887 @default.
• W2892087897 cites W1814874339 @default.
• W2892087897 cites W1822720520 @default.
• W2892087897 cites W1939978733 @default.
• W2892087897 cites W1969539549 @default.
• W2892087897 cites W1977268219 @default.
• W2892087897 cites W1979600880 @default.
• W2892087897 cites W1983351391 @default.
• W2892087897 cites W1989662265 @default.
• W2892087897 cites W1991972495 @default.
• W2892087897 cites W1993013617 @default.
• W2892087897 cites W1996457240 @default.
• W2892087897 cites W1997561098 @default.
• W2892087897 cites W2005443228 @default.
• W2892087897 cites W2009039680 @default.
• W2892087897 cites W2011186694 @default.
• W2892087897 cites W2012130794 @default.
• W2892087897 cites W2027939711 @default.
• W2892087897 cites W2028586311 @default.
• W2892087897 cites W2039829190 @default.
• W2892087897 cites W2041856304 @default.
• W2892087897 cites W2046638114 @default.
• W2892087897 cites W2055427508 @default.
• W2892087897 cites W2056502074 @default.
• W2892087897 cites W2072625253 @default.
• W2892087897 cites W2077171467 @default.
• W2892087897 cites W2087612350 @default.
• W2892087897 cites W2089383992 @default.
• W2892087897 cites W2090830582 @default.
• W2892087897 cites W2102837546 @default.
• W2892087897 cites W2107268345 @default.
• W2892087897 cites W2110210715 @default.
• W2892087897 cites W2123853229 @default.
• W2892087897 cites W2125490827 @default.
• W2892087897 cites W2125922540 @default.
• W2892087897 cites W2134450450 @default.
• W2892087897 cites W2134468110 @default.
• W2892087897 cites W2138581630 @default.
• W2892087897 cites W2140975775 @default.
• W2892087897 cites W2144071972 @default.
• W2892087897 cites W2147109509 @default.
• W2892087897 cites W2150156671 @default.
• W2892087897 cites W2154075930 @default.
• W2892087897 cites W2154555351 @default.
• W2892087897 cites W2165011175 @default.
• W2892087897 cites W2167376504 @default.
• W2892087897 cites W2167645403 @default.
• W2892087897 cites W2167719636 @default.
• W2892087897 cites W2266996646 @default.
• W2892087897 cites W2298232809 @default.
• W2892087897 cites W2305946377 @default.
• W2892087897 cites W2314704099 @default.
• W2892087897 cites W2339943063 @default.
• W2892087897 cites W2348392815 @default.
• W2892087897 cites W2398047035 @default.
• W2892087897 cites W2411473132 @default.
• W2892087897 cites W2518117171 @default.
• W2892087897 cites W2531684896 @default.
• W2892087897 cites W2551609604 @default.
• W2892087897 cites W2561178222 @default.
• W2892087897 cites W2586577682 @default.
• W2892087897 cites W2595234941 @default.
• W2892087897 cites W2613857725 @default.
• W2892087897 cites W2761936011 @default.
• W2892087897 cites W2773435384 @default.
• W2892087897 cites W2781673392 @default.
• W2892087897 cites W2790381216 @default.
• W2892087897 cites W2916183363 @default.
• W2892087897 doi "https://doi.org/10.3389/fcvm.2018.00125" @default.
• W2892087897 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6135907" @default.
• W2892087897 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30238007" @default.
• W2892087897 hasPublicationYear "2018" @default.
• W2892087897 type Work @default.
• W2892087897 sameAs 2892087897 @default.
• W2892087897 citedByCount "19" @default.
• W2892087897 countsByYear W28920878972019 @default.
• W2892087897 countsByYear W28920878972020 @default.
• W2892087897 countsByYear W28920878972021 @default.
• W2892087897 countsByYear W28920878972022 @default.
• W2892087897 countsByYear W28920878972023 @default.
• W2892087897 crossrefType "journal-article" @default.
• W2892087897 hasAuthorship W2892087897A5000786208 @default.
• W2892087897 hasAuthorship W2892087897A5003052748 @default.
• W2892087897 hasAuthorship W2892087897A5019846091 @default.
• W2892087897 hasAuthorship W2892087897A5030073630 @default.

• next