Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/44859
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Type: Journal article
Title: Molecular pathology of expanded polyalanine tract mutations in the Aristaless-related homeobox gene
Author: Shoubridge, C.
Cloosterman, D.
Parkinson-Lawrence, E.
Brooks, D.
Gecz, J.
Citation: Genomics, 2007; 90(1):59-71
Publisher: Academic Press Inc Elsevier Science
Issue Date: 2007
ISSN: 0888-7543
1089-8646
Statement of
Responsibility: 
Cheryl Shoubridge, Desiree Cloosterman, Emma Parkinson–Lawerence, Douglas Brooks and Jozef Gécz
Abstract: The Aristaless-related homeobox gene (ARX) is one of the major genes causing X-linked mental retardation. We have been interested in the pathogenic mechanism of expanded polyalanine tract mutations in ARX. We showed that the c.304ins(GCG)7 mutation causing an increase from 16 to 23 alanines increased the propensity of ARX protein aggregation and a shift from nuclear to cytoplasmic localization. We proposed that mislocalization of ARX via cytoplasmic aggregation and subsequent degradation leads to a partial loss of function, contributing to the pathogenesis. We identified importin 13 (IPO13), a mediator of nuclear import for a variety of proteins, as a novel ARX interacting protein. We predicted that the transport of ARX by IPO13 from the cytoplasm to the nucleus might be disrupted by expanded polyalanine tract mutations, but our data showed that in both yeast and mammalian cells these mutant ARX proteins were still able to interact with IPO13. We established the nuclear localization regions of the ARX homeodomain that were required for the interaction with IPO13 and correct localization of the full-length ARX transcription factor to the nucleus.
Keywords: Cell Line; Cell Line, Tumor; PC12 Cells; Cytoplasm; Animals; Humans; Rats; Mental Retardation, X-Linked; Peptides; Karyopherins; Homeodomain Proteins; Transcription Factors; Transfection; Cell Death; Amino Acid Sequence; Active Transport, Cell Nucleus; Mutation; Molecular Sequence Data
Description: Crown copyright © 2007 Published by Elsevier Inc.
RMID: 0020072374
DOI: 10.1016/j.ygeno.2007.03.005
Description (link): http://www.elsevier.com/wps/find/journaldescription.cws_home/622838/description#description
Appears in Collections:Paediatrics publications

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