Show simple item record

dc.contributor.authorMantovani, F
dc.contributor.authorTocco, F
dc.contributor.authorGirardini, J
dc.contributor.authorSmith, P
dc.contributor.authorGasco, M
dc.contributor.authorLu, X
dc.contributor.authorCrook, T
dc.contributor.authorDel Sal, G
dc.date.accessioned2018-08-30T15:03:29Z
dc.date.issued2007-10
dc.identifier10
dc.identifier.citationNATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 pp. 912 - 920
dc.identifier.issn1545-9993
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2474
dc.identifier.doi10.1038/nsmb1306
dc.description.abstractThe tumor-suppressor function of p53 relies on its transcriptional activity, which is modulated by post-translational modifications and interactions with regulatory proteins. The prolyl isomerase Pin1 has a central role in transducing phosphorylation of p53 into conformational changes that affect p53 stability and function. We found that Pin1 is required for efficient loading of p53 on target promoters upon stress. In addition, Pin1 is recruited to chromatin by p53 and stimulates binding of the p300 acetyltransferase and consequent p53 acetylation. Accordingly, tumor-associated mutations at Pin1-binding residues within the p53 proline-rich domain hamper acetylation of p53 by p300. After phosphorylation of p53 at Ser46 triggered by cytotoxic stimuli, Pin1 also mediates p53’s dissociation from the apoptosis inhibitor iASPP, promoting cell death. In tumors bearing wild-type p53, expression of Pin1 and iASPP are inversely correlated, supporting the clinical relevance of these interactions.
dc.format.extent912 - 920
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.titleThe prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP
dc.typeJournal Article
rioxxterms.versionofrecord10.1038/nsmb1306
rioxxterms.licenseref.startdate2007-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNATURE STRUCTURAL & MOLECULAR BIOLOGY
pubs.notesaffiliation: Del Sal, G (Reprint Author), Univ Trieste, Dipartimento Biochim Biofis & Chim Macromol, Lab Nazl Consorz Interuniv Biotechnol, Area Sci Pk, I-34100 Trieste, Italy. Univ Trieste, Dipartimento Biochim Biofis & Chim Macromol, Lab Nazl Consorz Interuniv Biotechnol, I-34100 Trieste, Italy. Breast Canc Res Ctr, Inst Canc Res, London SW3 6JB, England. Croce & Carle Hosp, Dept Med Oncol, I-12100 Cuneo, Italy. UCL, Ludwig Inst Canc Res, London W1W 7BS, England. keywords-plus: DNA-DEPENDENT ACETYLATION; INTERACTING PROTEIN KINASE-2; IN-VIVO; GENE-EXPRESSION; CELL-CYCLE; PHOSPHORYLATES P53; FUNCTIONAL DOMAIN; COACTIVATOR P300; ACTIVATION; BINDING research-areas: Biochemistry & Molecular Biology; Biophysics; Cell Biology web-of-science-categories: Biochemistry & Molecular Biology; Biophysics; Cell Biology author-email: [email protected] number-of-cited-references: 53 times-cited: 104 usage-count-last-180-days: 0 usage-count-since-2013: 3 journal-iso: Nat. Struct. Mol. Biol. doc-delivery-number: 221KR unique-id: ISI:000250226700013 da: 2018-08-30
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume14
pubs.embargo.termsNot known
dc.contributor.icrauthorCrook, Timothyen


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following collection(s)

Show simple item record