The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA interaction in vitro
dc.contributor.author | Kaur, Kawaljit | |
dc.contributor.author | Wu, Xiaoqing | |
dc.contributor.author | Fields, James K. | |
dc.contributor.author | Johnson, David K. | |
dc.contributor.author | Lan, Lan | |
dc.contributor.author | Pratt, Miranda | |
dc.contributor.author | Somoza, Amber D. | |
dc.contributor.author | Wang, Clay C. C. | |
dc.contributor.author | Karanicolas, John | |
dc.contributor.author | Oakley, Berl R. | |
dc.contributor.author | Liang, Xu | |
dc.contributor.author | De Guzman, Roberto N. | |
dc.date.accessioned | 2018-11-14T20:16:39Z | |
dc.date.available | 2018-11-14T20:16:39Z | |
dc.date.issued | 2017-04-17 | |
dc.identifier.citation | Kaur K, Wu X, Fields JK, Johnson DK, Lan L, Pratt M, et al. (2017) The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-R NA interaction in vitro. PLoS ONE 12(4): e0175471. https://doi.org/10.1371/journal.pone.0175471 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/27352 | |
dc.description.abstract | The RNA-binding protein Hu antigen R (HuR) binds to AU-rich elements (ARE) in the 3’-untranslated region (UTR) of target mRNAs. The HuR-ARE interactions stabilize many oncogenic mRNAs that play important roles in tumorigenesis. Thus, small molecules that interfere with the HuR-ARE interaction could potentially inhibit cancer cell growth and progression. Using a fluorescence polarization (FP) competition assay, we identified the compound azaphilone-9 (AZA-9) derived from the fungal natural product asperbenzaldehyde, binds to HuR and inhibits HuR-ARE interaction (IC50 ~1.2 μM). Results from surface plasmon resonance (SPR) verified the direct binding of AZA-9 to HuR. NMR methods mapped the RNA-binding interface of HuR and identified the involvement of critical RNA-binding residues in binding of AZA-9. Computational docking was then used to propose a likely binding site for AZA-9 in the RNA-binding cleft of HuR. Our results show that AZA-9 blocks key RNA-binding residues of HuR and disrupts HuR-RNA interactions in vitro. This knowledge is needed in developing more potent AZA-9 derivatives that could lead to new cancer therapy. | en_US |
dc.publisher | Public Library of Science | en_US |
dc.rights | © 2017 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.title | The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA interaction in vitro | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Kaur, Kawaljit | |
kusw.kuauthor | Wu, Xiaoqing | |
kusw.kuauthor | Johnson, David K. | |
kusw.kuauthor | Lan, Lan | |
kusw.kuauthor | Karanicolas, John | |
kusw.kuauthor | Oakley, Berl R. | |
kusw.kuauthor | Xu, Liang | |
kusw.kuauthor | De Guzman, Roberto N. | |
kusw.kudepartment | Molecular Biosciences | en_US |
kusw.kudepartment | Higuchi Biosciences Center | en_US |
dc.identifier.doi | 10.1371/journal.pone.0175471 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | en_US |
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Except where otherwise noted, this item's license is described as: © 2017 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.