Article abstract
Nature Cell Biology 10, 802 - 811 (2008)
Published online: 15 June 2008 | doi:10.1038/ncb1742
Genomic stability and tumour suppression by the APC/C cofactor Cdh1
Irene García-Higuera1,2, Eusebio Manchado1, Pierre Dubus3, Marta Cañamero4, Juan Méndez5, Sergio Moreno2 & Marcos Malumbres1
Abstract
The anaphase promoting complex or cyclosome (APC/C) is a ubiquitin protein ligase that, together with Cdc20 or Cdh1, targets cell-cycle proteins for degradation. APC/C–Cdh1 specifically promotes protein degradation in late mitosis and G1. Mutant embryos lacking Cdh1 die at E9.5–E10.5 due to defects in the endoreduplication of trophoblast cells and placental malfunction. This lethality is prevented when Cdh1 is expressed in the placenta. Cdh1-deficient cells proliferate inefficiently and accumulate numeric and structural chromosomal aberrations, indicating that Cdh1 contributes to the maintenance of genomic stability. Cdh1 heterozygous animals show increased susceptibility to spontaneous tumours, suggesting that Cdh1 functions as a haploinsufficient tumour suppressor. These heterozygous mice also show several defects in behaviour associated with increased proliferation of stem cells in the nervous system. These results indicate that Cdh1 is required for preventing unscheduled proliferation of specific progenitor cells and protecting mammalian cells from genomic instability.
- Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
- Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
- EA2406 University of Bordeaux 2, Bordeaux, France.
- Comparative Pathology Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
- DNA Replication Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Correspondence to: Marcos Malumbres1 e-mail: malumbres@cnio.es
Correspondence to: Sergio Moreno2 e-mail: smo@usal.es
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cellsThe EMBO Journal Article (15 Sep 2003)
Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cellsThe EMBO Journal Article (15 Sep 2003)
The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memoryNature Cell Biology Letter (01 Sep 2008)
See all 21 matches for Research
