TY  - JOUR
A1  - Straub, Wesley E.
A1  - Weber, Tobias Alexander
A1  - Schäfer, Birgit
A1  - Candi, Eleonora
A1  - Durst, Florian
A1  - Ou, Horng Der
A1  - Rajalingam, Krishnaraj
A1  - Melino, Gennaro
A1  - Dötsch, Volker
T1  - The C-terminus of p63 contains multiple regulatory elements with different functions
T2  - Cell death & disease
N2  - 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
KW  - p63
KW  - transcriptional regulation
KW  - auto-inhibition
KW  - sumoylation
Y1  - 2010
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7464
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-74403
SN  - 2041-4889
N1  - Cell Death and Disease is an open-access journal published by Nature Publishing Group. This article is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 license. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
VL  - 1
IS  - e5
SP  - 1
EP  - 8
PB  - Nature Publishing Group
CY  - London [u. a.]
ER  -