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dc.contributor.authorKaur, Kawaljit
dc.contributor.authorWu, Xiaoqing
dc.contributor.authorFields, James K.
dc.contributor.authorJohnson, David K.
dc.contributor.authorLan, Lan
dc.contributor.authorPratt, Miranda
dc.contributor.authorSomoza, Amber D.
dc.contributor.authorWang, Clay C. C.
dc.contributor.authorKaranicolas, John
dc.contributor.authorOakley, Berl R.
dc.contributor.authorLiang, Xu
dc.contributor.authorDe Guzman, Roberto N.
dc.date.accessioned2018-11-14T20:16:39Z
dc.date.available2018-11-14T20:16:39Z
dc.date.issued2017-04-17
dc.identifier.citationKaur 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.0175471en_US
dc.identifier.urihttp://hdl.handle.net/1808/27352
dc.description.abstractThe 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.publisherPublic Library of Scienceen_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.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleThe fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA interaction in vitroen_US
dc.typeArticleen_US
kusw.kuauthorKaur, Kawaljit
kusw.kuauthorWu, Xiaoqing
kusw.kuauthorJohnson, David K.
kusw.kuauthorLan, Lan
kusw.kuauthorKaranicolas, John
kusw.kuauthorOakley, Berl R.
kusw.kuauthorXu, Liang
kusw.kuauthorDe Guzman, Roberto N.
kusw.kudepartmentMolecular Biosciencesen_US
kusw.kudepartmentHiguchi Biosciences Centeren_US
kusw.oanotesPer SHERPA/RoMEO 11/14/18: Author's Pre-print: green tick author can archive pre-print (ie pre-refereeing) Author's Post-print: green tick author can archive post-print (ie final draft post-refereeing) Publisher's Version/PDF: green tick author can archive publisher's version/PDF General Conditions: Creative Commons Attribution License 4.0 Authors retain copyright Eligible UK authors may deposit in OpenDepot Publisher's version/PDF may be used Published source must be acknowledged with citation Author's pre-prints can be deposited in pre-print servers Publisher will deposit articles in PubMed Centralen_US
dc.identifier.doi10.1371/journal.pone.0175471en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
kusw.proid145856970752en_US
dc.rights.accessrightsopenAccessen_US


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© 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.
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.