Crosstalk between c-Jun and TAp73alpha/beta contributes to the apoptosis–survival balance

  • 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.

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Author:Max Koeppel, Simon J. van Heeringen, Daniela Kramer, Leonie Smeenk, Eva Janssen-Megens, Marianne Hartmann, Hendrik G. Stunnenberg, Marion Lohrum
URN:urn:nbn:de:hebis:30-106486
DOI:https://doi.org/10.1093/nar/gkr028
ISSN:1362-4962
ISSN:0305-1048
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/21459846
Parent Title (English):Nucleic acids research
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Language:English
Date of Publication (online):2011/08/13
Date of first Publication:2011/03/31
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2011/08/13
Volume:39
Issue:14
Page Number:17
First Page:6069
Last Page:6085
Note:
© 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.
Source:Nucleic acids research, 2011, 1–17 ; doi 10.1093/nar/gkr028
HeBIS-PPN:272953288
Institutes:Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0