CUL-4A Is Critical for Early Embryonic Development
AUTOR(ES)
Li, Binghui
FONTE
American Society for Microbiology
RESUMO
Ubiquitin-mediated degradation targets cell cycle regulators for proteolysis. Much of the ubiquitin pathway's substrate specificity is conferred by E3 ubiquitin ligases, and cullins are core components of some E3s. CUL-4A encodes one of six mammalian cullins and is amplified and/or overexpressed in breast cancer, which suggests a role in regulating cell cycle progression. To examine CUL-4A's physiologic function, we generated a CUL-4A deletion mutation in mice. No viable CUL-4A−/− pups and no homozygous mutant embryos as early as 7.5 days postcoitum (dpc) were recovered. However, CUL-4A−/− blastocysts are viable, hatch, form an inner cell mass and trophectoderm, and implant (roughly 4.5 dpc), indicating that CUL-4A−/− embryos die between 4.5 and 7.5 dpc. Despite 87% similarity between the Cul-4A and Cul-4B cullins, the CUL-4A−/− lethal phenotype indicates that CUL-4A has one or more distinct function(s). Surprisingly, 44% fewer heterozygous pups were recovered than expected by Mendelian genetics, indicating that many heterozygous embryos also die during gestation due to haploinsufficiency. Taken together, our findings indicate that appropriate CUL-4A expression is critical for early embryonic development.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=139768Documentos Relacionados
- CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein
- Miz1 Is Required for Early Embryonic Development during Gastrulation
- CpG Binding Protein Is Crucial for Early Embryonic Development
- Cse1l Is Essential for Early Embryonic Growth and Development
- Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor
