title: Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Arai
authors.forename: Jocelyn S
authors.initials: JS
authors.lastname: Kasper
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Skaar
authors.forename: Syed Hamid
authors.initials: SH
authors.lastname: Ali
authors.forename: Chiaki
authors.initials: C
authors.lastname: Takahashi
authors.forename: James A
authors.initials: JA
authors.lastname: DeCaprio
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001808:Blood Vessels / Q000002:abnormalities* / Q000196:embryology; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D044842:Cullin Proteins; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000473:pathology; D018390:Gene Targeting; D008025:Ligases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D010641:Phenotype; D010920:Placenta / Q000002:abnormalities / Q000098:blood supply; D011247:Pregnancy; D011485:Protein Binding
chemical_list: D018797:Cell Cycle Proteins; C494817:Cul7 protein, mouse; D044842:Cullin Proteins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D008025:Ligases