Sherwood Victoria, Manbodh Ria, Sheppard Carol, Chalmers Andrew D
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom.
Mol Biol Cell. 2008 Apr;19(4):1772-82. doi: 10.1091/mbc.e07-07-0652. Epub 2008 Feb 13.
Mitosis is a fundamental feature of all cellular organisms. It must be tightly regulated to allow normal tissue growth and to prevent cancer formation. Here, we identify a new protein that is required for mitosis. We show that the Ras association (RA) domain-containing protein, RASSF7, is part of an evolutionarily conserved group of four proteins. These are RASSF7, RASSF8, and two new RASSF proteins P-CIP1/RASSF9 and RASSF10. We call this group the N-terminal RASSF family. We analyzed the function of Xenopus RASSF7. RASSF7 was found to be expressed in several embryonic tissues including the skin, eyes, and neural tube. Knocking down its function led to cells failing to form a mitotic spindle and arresting in mitosis. This caused nuclear breakdown, apoptosis, and a striking loss of tissue architecture in the neural tube. Consistent with a role in spindle formation, RASSF7 protein was found to localize to the centrosome. This localization occurred in a microtubule-dependent manner, demonstrating that there is a mutually dependant relationship between RASSF7 localization and spindle formation. Thus RASSF7, the first member of the N-terminal RASSF family to be functionally analyzed, is a centrosome-associated protein required to form a spindle and complete mitosis in the neural tube.
有丝分裂是所有细胞生物的一个基本特征。它必须受到严格调控,以实现正常的组织生长并预防癌症形成。在此,我们鉴定出一种有丝分裂所需的新蛋白质。我们发现,含Ras关联(RA)结构域的蛋白质RASSF7是一个由四种蛋白质组成的进化保守基团的一部分。这四种蛋白质分别是RASSF7、RASSF8,以及两种新的RASSF蛋白质P-CIP1/RASSF9和RASSF10。我们将这个基团称为N端RASSF家族。我们分析了非洲爪蟾RASSF7的功能。发现RASSF7在包括皮肤、眼睛和神经管在内的几种胚胎组织中表达。敲低其功能会导致细胞无法形成有丝分裂纺锤体并停滞在有丝分裂期。这会导致核破裂、细胞凋亡以及神经管组织结构的显著丧失。与在纺锤体形成中的作用一致,发现RASSF7蛋白定位于中心体。这种定位以微管依赖的方式发生,表明RASSF7定位与纺锤体形成之间存在相互依赖的关系。因此,RASSF7作为N端RASSF家族中首个进行功能分析的成员,是一种与中心体相关的蛋白质,在神经管中形成纺锤体并完成有丝分裂所必需。