Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Sladky, VC; Knapp, K; Soratroi, C; Heppke, J; Eichin, F; Rocamora-Reverte, L; Szabo, TG; Bongiovanni, L; Westendorp, B; Moreno, E; van Liere, EA; Bakker, B; Spierings, DCJ; Wardenaar, R; Pereyra, D; Starlinger, P; Schultze, S; Trauner, M; Stojakovic, T; Scharnagl, H; Fava, LL; Foijer, F; de Bruin, A; Villunger, A.
E2F-Family Members Engage the PIDDosome to Limit Hepatocyte Ploidy in Liver Development and Regeneration.
Dev Cell. 2020; 52(3):335-349 Doi: 10.1016/j.devcel.2019.12.016
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Scharnagl Hubert; Stojakovic Tatjana
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: E2F transcription factors control the cytokinesis machinery and thereby ploidy in hepatocytes. If or how these proteins limit proliferation of polyploid cells with extra centrosomes remains unknown. Here, we show that the PIDDosome, a signaling platform essential for caspase-2-activation, limits hepatocyte ploidy and is instructed by the E2F network to control p53 in the developing as well as regenerating liver. Casp2 and Pidd1 act as direct transcriptional targets of E2F1 and its antagonists, E2F7 and E2F8, that together co-regulate PIDDosome expression during juvenile liver growth and regeneration. Of note, whereas hepatocyte aneuploidy correlates with the basal ploidy state, the degree of aneuploidy itself is not limited by PIDDosome-dependent p53 activation. Finally, we provide evidence that the same signaling network is engaged to control ploidy in the human liver after resection. Our study defines the PIDDosome as a primary target to manipulate hepatocyte ploidy and proliferation rates in the regenerating liver. Copyright © 2019 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Aneuploidy -; Animals -; CRADD Signaling Adaptor Protein - physiology; Caspase 2 - physiology; Centrosome -; Cyclin-Dependent Kinase Inhibitor p21 - physiology; Cytokinesis -; Death Domain Receptor Signaling Adaptor Proteins - physiology; E2F Transcription Factors - physiology; Female -; Hepatocytes - cytology; Hepatocytes - metabolism; Humans -; Liver Regeneration -; Male -; Mice -; Mice, Knockout -; Polyploidy -; Tumor Suppressor Protein p53 - physiology