Document Detail

The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors.
MedLine Citation:
PMID:  24301385     Owner:  NLM     Status:  In-Data-Review    
The E3-ubiquitin ligase APC/C-Cdh1 is essential for endoreduplication but its relevance in the mammalian mitotic cell cycle is still unclear. Here we show that genetic ablation of Cdh1 in the developing nervous system results in hypoplastic brain and hydrocephalus. These defects correlate with enhanced levels of Cdh1 substrates and increased entry into the S phase in neural progenitors. However, cell division is prevented in the absence of Cdh1 due to hyperactivation of cyclin-dependent kinases, replicative stress, induction of p53, G2 arrest and apoptotic death of these progenitor cells. Concomitant ablation of p53 rescues apoptosis but not replicative stress, resulting in the presence of damaged neurons throughout the adult brain. These data indicate that the inactivation of Cdh1 in vivo results in replicative stress, cell cycle arrest and cell death, supporting recent therapeutic proposals aimed to inhibit the APC/C in tumours.
Manuel Eguren; Eva Porlan; Eusebio Manchado; Irene García-Higuera; Marta Cañamero; Isabel Fariñas; Marcos Malumbres
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nature communications     Volume:  4     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  2880     Citation Subset:  IM    
Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain.
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