Functional Characterization of the OFD1 Protein Reveals a Nuclear Localization and Physical Interaction with Subunits of a Chromatin Remodeling Complex

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2007 Sep 1

PMID 17761535

Citations 43

Authors

Giovanna Giorgio

Mariaevelina Alfieri

Clelia Prattichizzo

Alessandro Zullo

Stefano Cairo

Brunella Franco

Affiliations

Soon will be listed here.

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.

Citing Articles

Conservation of OFD1 Protein Motifs: Implications for Discovery of Novel Interactors and the OFD1 Function.

Jagodzik P, Zietkiewicz E, Bukowy-Bieryllo Z Int J Mol Sci. 2025; 26(3).

PMID: 39940934 PMC: 11818881. DOI: 10.3390/ijms26031167.

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene, ofd1.

Ka H, Cho M, Kwon S, Mun S, Han S, Kim M Cell Biosci. 2023; 13(1):195.

PMID: 37898820 PMC: 10612314. DOI: 10.1186/s13578-023-01146-9.

Non-syndromic Retinal Degeneration Caused by Pathogenic Variants in Joubert Syndrome Genes.

Sangermano R, Galdikaite-Braziene E, Bujakowska K Adv Exp Med Biol. 2023; 1415:173-182.

PMID: 37440031 DOI: 10.1007/978-3-031-27681-1_26.

Autistic Behavior as Novel Clinical Finding in OFD1 Syndrome.

Papuc S, Erbescu A, Glangher A, Streata I, Riza A, Budisteanu M Genes (Basel). 2023; 14(2).

PMID: 36833254 PMC: 9957277. DOI: 10.3390/genes14020327.

A novel non-sense variant in the OFD1 gene caused Joubert syndrome.

Li C, Wang X, Li F, Ding H, Liu L, Xiong Y Front Genet. 2023; 13:1064762.

PMID: 36704348 PMC: 9871390. DOI: 10.3389/fgene.2022.1064762.

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