The C-terminus of p63 contains multiple regulatory elements with different functions

The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervi
The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation. We have carried out an extensive alanine scanning study to identify critical regions within the inhibitory domain. These experiments show that a stretch of ~13 amino acids is crucial for the binding function. Further, investigation of transcriptional activity and the intracellular level of mutants that cannot be sumoylated suggests that sumoylation reduces the concentration of p63. We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63. Keywords: p63, transcriptional regulation, auto-inhibition, sumoylation
show moreshow less

Download full text files

Export metadata

  • Export Bibtex
  • Export RIS

Additional Services

    Share in Twitter Search Google Scholar
Metadaten
Author:Wesley E. Straub, Tobias Alexander Weber, Birgit Schäfer, Eleonora Candi, Florian Durst, Horng Der Ou, Krishnaraj Rajalingam, Gennaro Melino, Volker Dötsch
URN:urn:nbn:de:hebis:30-74403
DOI:http://dx.doi.org/10.1038/cddis.2009.1
ISBN:2041-4889
Parent Title (English):Cell Death and Disease
Publisher:Nature Publishing Group
Place of publication:London [u.a.]
Document Type:Article
Language:English
Date of Publication (online):2010/01/27
Year of first Publication:2010
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2010/01/27
Tag:auto-inhibition ; p63 ; sumoylation; transcriptional regulation
Issue:e5
Pagenumber:1
Note:
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.
HeBIS PPN:221157794
Institutes:Biochemie und Chemie
Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0

$Rev: 11761 $