RRC ID 32586
Author Ozaki H, Watanabe Y, Ikeda K, Kawakami K.
Title Impaired interactions between mouse Eyal harboring mutations found in patients with branchio-oto-renal syndrome and Six, Dach, and G proteins.
Journal J Hum Genet
Abstract Mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome as well as for other ocular defects. Most of the mutations are located within or in the vicinity of the EYA domain, which is highly conserved in the EYA protein family. The EYA domain is required for protein-protein interactions, which are important to the biological function of EYA proteins. To determine how EYA1 mutations cause BOR syndrome and/or ocular defects, we tested the effects of Eya1 mutations on interactions with Six. Dach, and G proteins by mammalian two-hybrid and GST-pulldown assays. Defective interactions were noted between BOR-type mutations S486P and L504R of Eya1 and Dach1, G proteins, and some Six proteins. These mutations impaired the activation of transcription from a Six-responsive gene, myogenin, with Six5. S486P and L504R showed an altered digestion pattern with trypsin, and L504R also decreased the sensitivity to V8 protease digestion and produced a peptide fragment with a different M(r). Our results suggest that defective protein-protein interactions of the mutations in the EYA domain underlie BOR syndrome and that SIX, DACH, and/or G proteins are possibly involved in the pathogenic processes.
Volume 47(3)
Pages 107-16
Published 2002-1-1
DOI 10.1007/s100380200011
PMID 11950062
MeSH Amino Acid Substitution Animals Branchio-Oto-Renal Syndrome / genetics* Branchio-Oto-Renal Syndrome / physiopathology DNA Mutational Analysis Drosophila Proteins* Endopeptidases GTP-Binding Proteins / genetics* GTP-Binding Proteins / physiology Gene Expression Regulation Genes, Reporter Humans Intracellular Signaling Peptides and Proteins Mice Mutation* Myogenin / physiology Nuclear Proteins / genetics* Nuclear Proteins / physiology Protein Structure, Tertiary / genetics Protein Structure, Tertiary / physiology Protein Tyrosine Phosphatases Trans-Activators / genetics* Trans-Activators / physiology Two-Hybrid System Techniques
IF 2.831
Times Cited 40
DNA material pf Six1 (RDB05730)