Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis.

Cul1, a member of the cullin ubiquitin ligase family, forms a multiprotein complex known as SCF and plays an essential role in numerous cellular and biological activities. A Cul1 homologue, p185 (Cul7), has been isolated as an simian virus 40 large T antigen-binding protein. To understand the physiological role of ...
p185, we generated mice lacking p185. p185-/- embryos are runted and die immediately after birth because of respiratory distress. Dermal and hypodermal hemorrhage is detected in mutant embryos at late gestational stage. p185-/- placentas show defects in the differentiation of the trophoblast lineage with an abnormal vascular structure. We demonstrate that p185 forms an SCF-like complex with Skp1, Rbx1, Fbw6 (Fbx29), and FAP68 (FAP48, glomulin). FAP68 has recently been identified as a gene responsible for familial glomuvenous malformation. These results suggest that p185 forms a multiprotein complex and plays an important role in vascular morphogenesis.
Mesh Terms:
Animals, Animals, Newborn, Blood Vessels, Cell Cycle Proteins, Cullin Proteins, Female, Fetal Growth Retardation, Gene Targeting, Ligases, Macromolecular Substances, Mice, Mice, Inbred C57BL, Mice, Knockout, Multiprotein Complexes, Phenotype, Placenta, Pregnancy, Protein Binding
Proc. Natl. Acad. Sci. U.S.A.
Date: Aug. 19, 2003
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