%0 Journal Article
%A Ahmed, Syed Moiz
%A Ragunathan, Priya
%A Shin, Joon
%A Peter, Sabrina
%A Kleissle, Sabrina
%A Neuenschwander, Martin
%A Schäfer, Reinhold
%A V Kries, Jens Peter
%A Grüber, Gerhard
%A Dröge, Peter
%T The FGFR inhibitor PD173074 binds to the C-terminus of oncofetal HMGA2 and modulates its DNA-binding and transcriptional activation functions.
%J FEBS letters
%V 597
%N 15
%@ 0014-5793
%C Chichester
%I Wiley
%M DKFZ-2023-01079
%P 1977-1988
%D 2023
%Z 2023 Aug;597(15):1977-1988
%X The architectural chromatin factor high-mobility group AT-hook 2 (HMGA2) is causally involved in several human malignancies and pathologies. HMGA2 is not expressed in most normal adult somatic cells, which renders the protein an attractive drug target. An established cell-based compound library screen identified the fibroblast growth factor receptor (FGFR) inhibitor PD173074 as an antagonist of HMGA2-mediated transcriptional reporter gene activation. We determined that PD173074 binds the C-terminus of HMGA2 and interferes with functional coordination of the three AT-hook DNA-binding domains mediated by the C-terminus. The HMGA2-antagonistic effect of PD173074 on transcriptional activation may therefore result from an induced altered DNA-binding mode of HMGA2. PD173074 as a novel HMGA2-specific antagonist could trigger the development of derivates with enhanced attributes and clinical potential.
%K AT-hook domain (Other)
%K C-terminal domain (Other)
%K FGFR inhibitor (Other)
%K HMGA2, small molecule antagonist (Other)
%K PD173074 (Other)
%K chromatin architectural factor (Other)
%K transcriptional regulator (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37259564
%R 10.1002/1873-3468.14675
%U https://inrepo02.dkfz.de/record/276370