TY  - JOUR
A1  - Koeppel, Max
A1  - Heeringen, Simon J. van
A1  - Kramer, Daniela
A1  - Smeenk, Leonie
A1  - Janssen-Megens, Eva
A1  - Hartmann, Marianne
A1  - Stunnenberg, Hendrik G.
A1  - Lohrum, Marion
T1  - Crosstalk between c-Jun and TAp73alpha/beta contributes to the apoptosis–survival balance
T2  - Nucleic acids research
N2  - The p53-family member p73 plays a role in various cellular signaling pathways during development and growth control and it can have tumor suppressor properties. Several isoforms of p73 exist with considerable differences in their function. Whereas the functions of the N-terminal isoforms (TA and delta Np73) and their opposing pro- and antiapoptotic roles have become evident, the functional differences of the distinct C-terminal splice forms of TAp73 have remained unclear. Here, we characterized the global genomic binding sites for TAp73alpha and TAp73beta by chromatin immunoprecipitation sequencing as well as the transcriptional responses by performing RNA sequencing. We identified a specific p73 consensus binding motif and found a strong enrichment of AP1 motifs in close proximity to binding sites for TAp73alpha. These AP1 motif-containing target genes are selectively upregulated by TAp73alpha, while their mRNA expression is repressed upon TAp73beta induction. We show that their expression is dependent on endogenous c-Jun and that recruitment of c-Jun to the respective AP1 sites was impaired upon TAp73beta expression, in part due to downregulation of c-Jun. Several of these AP1-site containing TAp73alpha-induced genes impinge on apoptosis induction, suggesting an underlying molecular mechanism for the observed functional differences between TAp73alpha and TAp73beta.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22412
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-106486
SN  - 1362-4962
SN  - 0305-1048
N1  - © The Author(s) 2011. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 39
IS  - 14
SP  - 6069
EP  - 6085
PB  - Oxford Univ. Press
CY  - Oxford
ER  -