| First Author | Li B | Year | 2002 |
| Journal | Mol Cell Biol | Volume | 22 |
| Issue | 14 | Pages | 4997-5005 |
| PubMed ID | 12077329 | Mgi Jnum | J:78032 |
| Mgi Id | MGI:2183132 | Doi | 10.1128/MCB.22.14.4997-5005.2002 |
| Citation | Li B, et al. (2002) CUL-4A is critical for early embryonic development. Mol Cell Biol 22(14):4997-5005 |
| abstractText | 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. |
