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Regulation of the Activity in the p53 Family Depends on the Organization of the Transactivation Domain.

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cam.issuedOnline2018-06-28
dc.contributor.authorKrauskopf, Katharina
dc.contributor.authorGebel, Jakob
dc.contributor.authorKazemi, Sina
dc.contributor.authorTuppi, Marcel
dc.contributor.authorLöhr, Frank
dc.contributor.authorSchäfer, Birgit
dc.contributor.authorKoch, Joachim
dc.contributor.authorGüntert, Peter
dc.contributor.authorDötsch, Volker
dc.contributor.authorKehrloesser, Sebastian
dc.contributor.orcidKehrloesser, Sebastian [0000-0002-6791-2421]
dc.date.accessioned2018-10-08T10:19:20Z
dc.date.available2018-10-08T10:19:20Z
dc.date.issued2018-08-07
dc.description.abstractDespite high sequence homology among the p53 family members, the regulation of their transactivation potential is based on strikingly different mechanisms. Previous studies revealed that the activity of TAp63α is regulated via an autoinhibitory mechanism that keeps inactive TAp63α in a dimeric conformation. While all p73 isoforms are constitutive tetramers, their basal activity is much lower compared with tetrameric TAp63. We show that the dimeric state of TAp63α not only reduces DNA binding affinity, but also suppresses interaction with the acetyltransferase p300. Exchange of the transactivation domains is sufficient to transfer the regulatory characteristics between p63 and p73. Structure determination of the transactivation domains of p63 and p73 in complex with the p300 Taz2 domain further revealed that, in contrast to p53 and p73, p63 has a single transactivation domain. Sequences essential for stabilizing the closed dimer of TAp63α have evolved into a second transactivation domain in p73 and p53.
dc.description.sponsorshipThe research was funded by the DFG (DO 545/8 and DO 545/13), the Center for Biomolecular Magnetic Resonance (BMRZ), and the Cluster of Excellence Frankfurt (Macromolecular Complexes). M.T. was supported by a fellowship from the Fonds of the Chemical Industry.
dc.identifier.doi10.17863/CAM.30591
dc.identifier.eissn1878-4186
dc.identifier.issn0969-2126
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283223
dc.languageeng
dc.language.isoeng
dc.publisherElsevier
dc.publisher.urlhttp://dx.doi.org/10.1016/j.str.2018.05.013
dc.subjectCBP
dc.subjectautoinhibition
dc.subjectoligomerization
dc.subjectp300
dc.subjectp53 family
dc.subjectp63
dc.subjectp73
dc.titleRegulation of the Activity in the p53 Family Depends on the Organization of the Transactivation Domain.
dc.typeArticle
dcterms.dateAccepted2018-05-17
prism.endingPage1100.e4
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNameStructure
prism.startingPage1091
prism.volume26
rioxxterms.licenseref.startdate2018-08-07
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1016/j.str.2018.05.013

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