Functional characterization of the OFD1 protein reveals a nuclear localization and physical interaction with Subunits of a chromatin remodeling complex

被引:66
作者
Giorgio, Giovanna
Alfieri, Mariaevelina
Prattichizzo, Clelia
Zullo, Alessandro
Cairo, Stefano
Franco, Brunella [1 ]
机构
[1] Telethon Inst Genet & Med, I-80131 Naples, Italy
[2] Univ Naples Federico 2, Dept Pediat, I-80131 Naples, Italy
关键词
D O I
10.1091/mbc.E07-03-0198
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:4397 / 4404
页数:8
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