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- W1999367215 endingPage "e90275" @default.
- W1999367215 startingPage "e90275" @default.
- W1999367215 abstract "Signal transducer and activator of transcription STAT5 and its upstream activating kinase JAK2 are essential mediators of cytokine signaling. Their activity is normally tightly regulated and transient. However, constitutive activation of STAT5 is found in numerous cancers and a driving force for malignant transformation. We describe here the identification of the synthetic chalcone α-Br-2′,3,4,4′-tetramethoxychalcone (α-Br-TMC) as a novel JAK/STAT inhibitor. Using the non-transformed IL-3-dependent B cell line Ba/F3 and its oncogenic derivative Ba/F3-1*6 expressing constitutively activated STAT5, we show that α-Br-TMC targets the JAK/STAT pathway at multiple levels, inhibiting both JAK2 and STAT5 phosphorylation. Moreover, α-Br-TMC alters the mobility of STAT5A/B proteins in SDS-PAGE, indicating a change in their post-translational modification state. These alterations correlate with a decreased association of STAT5 and RNA polymerase II with STAT5 target genes in chromatin immunoprecipitation assays. Interestingly, expression of STAT5 target genes such as Cis and c-Myc was differentially regulated by α-Br-TMC in normal and cancer cells. While both genes were inhibited in IL-3-stimulated Ba/F3 cells, expression of the oncogene c-Myc was down-regulated and that of the tumor suppressor gene Cis was up-regulated in transformed Ba/F3-1*6 cells. The synthetic chalcone α-Br-TMC might therefore represent a promising novel anticancer agent for therapeutic intervention in STAT5-associated malignancies." @default.
- W1999367215 created "2016-06-24" @default.
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- W1999367215 date "2014-03-03" @default.
- W1999367215 modified "2023-10-17" @default.
- W1999367215 title "The Synthetic α-Bromo-2′,3,4,4′-Tetramethoxychalcone (α-Br-TMC) Inhibits the JAK/STAT Signaling Pathway" @default.
- W1999367215 cites W149279734 @default.
- W1999367215 cites W1917578864 @default.
- W1999367215 cites W1964614068 @default.
- W1999367215 cites W1964691336 @default.
- W1999367215 cites W1968362887 @default.
- W1999367215 cites W1968885796 @default.
- W1999367215 cites W1969376484 @default.
- W1999367215 cites W1980155183 @default.
- W1999367215 cites W1981155770 @default.
- W1999367215 cites W1981745443 @default.
- W1999367215 cites W1983974405 @default.
- W1999367215 cites W1986922586 @default.
- W1999367215 cites W1989957102 @default.
- W1999367215 cites W1993034428 @default.
- W1999367215 cites W1996740511 @default.
- W1999367215 cites W1997965188 @default.
- W1999367215 cites W2001158436 @default.
- W1999367215 cites W2003535009 @default.
- W1999367215 cites W2004068229 @default.
- W1999367215 cites W2008409819 @default.
- W1999367215 cites W2009278160 @default.
- W1999367215 cites W2015645056 @default.
- W1999367215 cites W2018950591 @default.
- W1999367215 cites W2024282024 @default.
- W1999367215 cites W2029169197 @default.
- W1999367215 cites W2030182945 @default.
- W1999367215 cites W2031439970 @default.
- W1999367215 cites W2033753214 @default.
- W1999367215 cites W2036153681 @default.
- W1999367215 cites W2036286713 @default.
- W1999367215 cites W2041341438 @default.
- W1999367215 cites W2044219252 @default.
- W1999367215 cites W2044430082 @default.
- W1999367215 cites W2044559973 @default.
- W1999367215 cites W2046982014 @default.
- W1999367215 cites W2047398915 @default.
- W1999367215 cites W2051577500 @default.
- W1999367215 cites W2058451029 @default.
- W1999367215 cites W2060402899 @default.
- W1999367215 cites W2065238506 @default.
- W1999367215 cites W2070597688 @default.
- W1999367215 cites W2070658555 @default.
- W1999367215 cites W2076752985 @default.
- W1999367215 cites W2082745597 @default.
- W1999367215 cites W2089914453 @default.
- W1999367215 cites W2090371347 @default.
- W1999367215 cites W2091069088 @default.
- W1999367215 cites W2093234844 @default.
- W1999367215 cites W2095715114 @default.
- W1999367215 cites W2104830066 @default.
- W1999367215 cites W2105550924 @default.
- W1999367215 cites W2107077050 @default.
- W1999367215 cites W2110378711 @default.
- W1999367215 cites W2112716376 @default.
- W1999367215 cites W2112953655 @default.
- W1999367215 cites W2113890278 @default.
- W1999367215 cites W2115186999 @default.
- W1999367215 cites W2119456915 @default.
- W1999367215 cites W2119802871 @default.
- W1999367215 cites W2124674978 @default.
- W1999367215 cites W2127048642 @default.
- W1999367215 cites W2127663041 @default.
- W1999367215 cites W2128124948 @default.
- W1999367215 cites W2129024737 @default.
- W1999367215 cites W2130148894 @default.
- W1999367215 cites W2134540087 @default.
- W1999367215 cites W2137605946 @default.
- W1999367215 cites W2138807703 @default.
- W1999367215 cites W2146784178 @default.
- W1999367215 cites W2151465682 @default.
- W1999367215 cites W2154279096 @default.
- W1999367215 cites W2155357606 @default.
- W1999367215 cites W2157930170 @default.
- W1999367215 cites W2160946368 @default.
- W1999367215 cites W2162384201 @default.
- W1999367215 cites W2168683010 @default.
- W1999367215 cites W2168964329 @default.
- W1999367215 cites W2224782492 @default.
- W1999367215 cites W2423833205 @default.
- W1999367215 cites W4211210715 @default.
- W1999367215 cites W4239139991 @default.
- W1999367215 cites W4553897 @default.
- W1999367215 doi "https://doi.org/10.1371/journal.pone.0090275" @default.
- W1999367215 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3940872" @default.
- W1999367215 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24595334" @default.