Functional characterization of the OFD1 protein reveals a nuclear localization and physical interaction with Subunits of a chromatin remodeling complex
Functional characterization of the OFD1 protein reveals a nuclear localization and physical interaction with Subunits of a chromatin remodeling complex
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DOI：
10.1091/mbc.e07-03-0198
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发表时间：
2007-11-01
影响因子：
3.3
通讯作者：
Franco, Brunella
中科院分区：
文献类型：
--
作者：
Giorgio, Giovanna;Alfieri, Mariaevelina;Franco, Brunella
口-面-指（OFD）I型综合征是一种X连锁显性遗传疾病（MIM 311200），其特征是口腔、面部和手指畸形以及囊性肾脏。我们以前确定OFD 1，这种疾病的基因负责，它编码一个中心体蛋白与未知的功能。我们现在报告OFD 1定位于初级纤毛和细胞核。此外，我们证明OFD 1蛋白能够自我关联，这种相互作用是由其卷曲螺旋丰富的区域介导的。有趣的是，我们确定了一个OFD 1相互作用蛋白RuvB 11，一种属于AAA（+）-家族的ATP酶，最近已与斑马鱼的囊性肾和纤毛装配和功能在莱茵衣藻。我们还提供了实验证据，OFD 1，连同RUVB 11，能够与人类TIP 60组蛋白乙酰转移酶（HAT）多亚基复合物的亚基共免疫沉淀。在这些结果的基础上，我们推测OFD 1可能是一个多蛋白复合物的一部分，可以发挥不同的生物学功能，在中心体初级纤毛细胞器以及在核隔室。
Oral-facial-digital (OFD) type I syndrome is an X-linked dominant disease (MIM311200) characterized by malformations of oral cavity, face, and digits and by cystic kidneys. We previously identified OFD1, the gene responsible for this disorder, which encodes for a centrosomal protein with an unknown function. We now report that OFD1 localizes both to the primary cilium and to the nucleus. Moreover, we demonstrate that the OFD1 protein is able to self-associate and that this interaction is mediated by its coiled-coil rich region. Interestingly, we identify an OFD1-interacting protein RuvBl1, a protein belonging to the AAA(+)-family of ATPases, which has been recently associated to cystic kidney in zebrafish and to ciliary assembly and function in Chlamydomonas reinhardtii. We also provide experimental evidence that OFD1, together with RUVBl1, is able to coimmunoprecipitate with subunits of the human TIP60 histone acetyltransferase (HAT) multisubunit complex. On the basis of these results, we hypothesize that OFD1 may be part of a multi-protein complex and could play different biological functions in the centrosome-primary cilium organelles as well as in the nuclear compartment.