The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults

Paola Zacchi, Monica Gostissa, Takafumi Uchida, Clio Salvagno, Fabio Avolio, Stefano Volinia, Ze'ev Ronai, Giovanni Blandino, Claudio Schneider and Giannino Del Sal ()
Additional contact information
Paola Zacchi: Laboratorio Nazionale CIB, AREA Science Park
Monica Gostissa: Laboratorio Nazionale CIB, AREA Science Park
Takafumi Uchida: Tohoku University
Clio Salvagno: Laboratorio Nazionale CIB, AREA Science Park
Fabio Avolio: Laboratorio Nazionale CIB, AREA Science Park
Stefano Volinia: Universita' di Ferrara, Sezione di Istologia ed Embriologia, Dipartimento di Morfologia ed Embriologia
Ze'ev Ronai: One Gustave L. Levy Place
Giovanni Blandino: Regina Elena Cancer Institute
Claudio Schneider: Laboratorio Nazionale CIB, AREA Science Park
Giannino Del Sal: Laboratorio Nazionale CIB, AREA Science Park

Nature, 2002, vol. 419, issue 6909, 853-857

Abstract: Abstract The tumour suppressor p53 is important in the cell decision to either arrest cell cycle progression or induce apoptosis in response to a variety of stimuli. p53 post-translational modifications and association with other proteins have been implicated in the regulation of its stability and transcriptional activities1,2. Here we report that, on DNA damage, p53 interacts with Pin1, a peptidyl-prolyl isomerase3, which regulates the function of many proteins involved in cell cycle control and apoptosis4,5,6. The interaction is strictly dependent on p53 phosphorylation, and requires Ser 33, Thr 81 and Ser 315. On binding, Pin1 generates conformational changes in p53, enhancing its transactivation activity. Stabilization of p53 is impaired in UV-treated Pin1-/- cells owing to its inability to efficiently dissociate from Mdm2. As a consequence, a reduced p53-dependent response was detected in Pin1-/- cells, and this correlates with a diminished transcriptional activation of some p53-regulated genes. Our results suggest that, following stress-induced phosphorylation, p53 needs to form a complex with Pin1 and to undergo a conformational change to fulfil its biological roles.

Date: 2002
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01120 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:419:y:2002:i:6909:d:10.1038_nature01120

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01120

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().