title: Functional characterization of the OFD1 protein reveals a nuclear localization and physical interaction with subunits of a chromatin remodeling complex.
abstract: 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.
authors.affiliation: Telethon Institute of Genetics and Medicine, 80131 Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgio
authors.forename: Mariaevelina
authors.initials: M
authors.lastname: Alfieri
authors.forename: Clelia
authors.initials: C
authors.lastname: Prattichizzo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zullo
authors.forename: Stefano
authors.initials: S
authors.lastname: Cairo
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002923:Cilia / Q000378:metabolism; D004285:Dogs; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; C115130:OFD1 protein, human; D021122:Protein Subunits; D011506:Proteins; D051548:Histone Acetyltransferases; D000251:Adenosine Triphosphatases