Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis
Open accessAbstract
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.
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CUL7 plays a role in vascular morphogenesis.
“CUL7 plays a role in vascular morphogenesis (Arai et al., 2003).”
From Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears (2014) · cites this paper as Arai et al., 2003
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References 41 · Cited by 145
- Authors
- Arai, T., Kasper, J. S., Skaar, J. R., Ali, S. H., Takahashi, C., & DeCaprio, J. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-08-06
- Volume
- 100
- Issue
- 17
- Pages
- 9855-9860
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC187864
- OpenAlex
- W2031830082
- Cited by
- 145
- References
- 41
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 11 · 2019: 7 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 7 · 2014: 10 · 2013: 8 · 2012: 13
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA093804)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- SCF ubiquitin ligase, vascular morphogenesis, embryonic lethality, trophoblast differentiation, placentation, glomuvenous malformation, Skp1, RBX1, ubiquitin ligase complex
- MeSH terms
- Animals, Animals, Newborn, Blood Vessels, Female, Fetal Growth Retardation, Ligases, Mice, Inbred C57BL, Phenotype, Placenta, Pregnancy, Protein Binding, Mice, Knockout, Gene Targeting, Cell Cycle Proteins, Cullin Proteins, Macromolecular Substances, Multiprotein Complexes, Mice
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