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

Takehiro Arai, Jocelyn S. Kasper, Jeffrey R. Skaar, Syed Hamid Ali, Chiaki Takahashi, James A. DeCaprio

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9855-9860
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number17
DOIs
Publication statusPublished - Aug 19 2003
Externally publishedYes

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Multiprotein Complexes
Morphogenesis
Blood Vessels
Embryonic Structures
Cullin Proteins
Simian virus 40
Viral Tumor Antigens
Trophoblasts
Ligases
Ubiquitin
Placenta
Genes
Carrier Proteins
Parturition
Hemorrhage
Skin
Glomus vagale tumors

ASJC Scopus subject areas

  • Genetics
  • General

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Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis. / Arai, Takehiro; Kasper, Jocelyn S.; Skaar, Jeffrey R.; Ali, Syed Hamid; Takahashi, Chiaki; DeCaprio, James A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 17, 19.08.2003, p. 9855-9860.

Research output: Contribution to journalArticle

Arai, Takehiro ; Kasper, Jocelyn S. ; Skaar, Jeffrey R. ; Ali, Syed Hamid ; Takahashi, Chiaki ; DeCaprio, James A. / Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 17. pp. 9855-9860.
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