Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis
Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis
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DOI：
10.1073/pnas.1733908100
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发表时间：
2003-08-19
影响因子：
11.1
通讯作者：
DeCaprio, JA
中科院分区：
文献类型：
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作者：
Arai, T;Kasper, JS;DeCaprio, JA
Cul 1是cullin泛素连接酶家族的成员，形成一种称为SCF的多蛋白复合物，在许多细胞和生物学活动中起着重要作用。Cull同源物p185（Cul 7）已被分离为猴病毒40大T抗原结合蛋白。为了了解p185的生理作用，我们产生了缺乏p185的小鼠。p185（-/-）胚胎发育不良，出生后立即因呼吸窘迫而死亡。在妊娠晚期的突变胚胎中检测到皮肤和皮下出血。p185（-/-）胎盘显示滋养层谱系分化缺陷，具有异常的血管结构。我们证明了p185与Skp 1，Rbx 1，Fbw 6（Fbx 29）和FAP 68（FAP 48，球蛋白）形成SCF样复合物。FAP 68最近被鉴定为引起家族性血管球静脉畸形的基因。这些结果表明，p185形成一个多蛋白复合物，并在血管形态发生中发挥重要作用。
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 Cull 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.