PABPN1 overexpression leads to upregulation of genes encoding nuclear proteins that are sequestered in oculopharyngeal muscular dystrophy nuclear inclusions

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DOIResolve DOI: http://doi.org/10.1016/j.nbd.2004.10.019
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TypeArticle
Journal titleNeurobiology of Disease
Volume18
Issue3
Pages551567; # of pages: 17
Subjectbio; Genes; Muscular Dystrophies; Protein; Proteins
AbstractOculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease caused by expanded (GCN)12–17 stretches encoding the Nterminal polyalanine domain of the poly(A) binding protein nuclear 1 (PABPN1). OPMD is characterized by intranuclear inclusions (INIs) in skeletal muscle fibers, which contain PABPN1, molecular chaperones, ubiquitin, proteasome subunits, and poly(A)-mRNA. We describe an adenoviral model of PABPN1 expression that produces INIs in most cells. Microarray analysis revealed that PABPN1 overexpression reproducibly changed the expression of 202 genes. Sixty percent of upregulated genes encode nuclear proteins, including many RNA and DNA binding proteins. Immunofluorescence microscopy revealed that all tested nuclear proteins encoded by eight upregulated genes colocalize with PABPN1 within the INIs: CUGBP1, SFRS3, FKBP1A, HMG2, HNRPA1, PRC1, S100P, and HSP70. In addition, CUGBP1, SFRS3, and FKBP1A were also found in OPMD muscle INIs. This study demonstrates that a large number of nuclear proteins are sequestered in OPMD INIs, which may compromise cellular function.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedNo
NRC number47759
NPARC number3538842
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Record identifier761c638a-9238-4122-83a1-d96da6d7c82d
Record created2009-03-01
Record modified2016-05-09
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