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dc.contributor.authorHiraki, Masatsugu
dc.contributor.authorHwang, So-Young
dc.contributor.authorCao, Shugeng
dc.contributor.authorRamadhar, Timothy R.
dc.contributor.authorByun, Sanguine
dc.contributor.authorYoon, Kyoung Wan
dc.contributor.authorLee, Jung Hyun
dc.contributor.authorChu, Kiki
dc.contributor.authorGurkar, Aditi U.
dc.contributor.authorKolev, Vihren
dc.contributor.authorZhang, Jianming
dc.contributor.authorNamba, Takushi
dc.contributor.authorMurphy, Maureen E.
dc.contributor.authorNewman, David J.
dc.contributor.authorClardy, Jon
dc.contributor.authorLee, Samuel W.
dc.contributor.authorMandinova, Anna
dc.date.accessioned2017-04-11T19:27:29Z
dc.date.available2017-04-11T19:27:29Z
dc.date.issued2015-08
dc.date.submitted2015-06
dc.identifier.issn1074-5521
dc.identifier.urihttp://hdl.handle.net/1721.1/108058
dc.description.abstractTP53 is the most frequently mutated gene in human cancer, and small-molecule reactivation of mutant p53 function represents an important anticancer strategy. A cell-based, high-throughput small-molecule screen identified chetomin (CTM) as a mutant p53 R175H reactivator. CTM enabled p53 to transactivate target genes, restored MDM2 negative regulation, and selectively inhibited the growth of cancer cells harboring mutant p53 R175H in vitro and in vivo. We found that CTM binds to Hsp40 and increases the binding capacity of Hsp40 to the p53 R175H mutant protein, causing a potential conformational change to a wild-type-like p53. Thus, CTM acts as a specific reactivator of the p53 R175H mutant form through Hsp40. These results provide new insights into the mechanism of reactivation of this specific p53 mutant.en_US
dc.description.sponsorshipUnited States. National Institutes of Health (GM108415)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (CA142805)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (CA149477)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (CA80058)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (GM086258)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.chembiol.2015.07.016en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleSmall-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axisen_US
dc.typeArticleen_US
dc.identifier.citationHiraki, Masatsugu; Hwang, So-Young; Cao, Shugeng; Ramadhar, Timothy R.; Byun, Sanguine; Yoon, Kyoung Wan; Lee, Jung Hyun; et al. “Small-Molecule Reactivation of Mutant P53 to Wild-Type-Like P53 through the P53-Hsp40 Regulatory Axis.” Chemistry & Biology 22, no. 9 (September 2015): 1206–1216. © 2015 Elsevier Ltden_US
dc.contributor.departmentBroad Institute of MIT and Harvarden_US
dc.contributor.mitauthorLee, Samuel W.
dc.contributor.mitauthorMandinova, Anna
dc.relation.journalChemistry and Biologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHiraki, Masatsugu; Hwang, So-Young; Cao, Shugeng; Ramadhar, Timothy R.; Byun, Sanguine; Yoon, Kyoung Wan; Lee, Jung Hyun; Chu, Kiki; Gurkar, Aditi U.; Kolev, Vihren; Zhang, Jianming; Namba, Takushi; Murphy, Maureen E.; Newman, David J.; Mandinova, Anna; Clardy, Jon; Lee, Sam W.en_US
dspace.embargo.termsNen_US
mit.licensePUBLISHER_CCen_US


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