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

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1016/j.nbd.2004.10.019
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Name affiliation
  1. National Research Council of Canada. NRC Biotechnology Research Institute
FormatText, Article
Subjectbiotechnology; Genes; Muscular Dystrophies; Protein; Proteins
Abstract
Oculopharyngeal 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.
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In
  • Neurobiology of Disease 18, no. 3 (April 2005): 551–567.
LanguageEnglish
NRC number47759
NPARC number3538842
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Record identifier761c638a-9238-4122-83a1-d96da6d7c82d
Record created2009-03-01
Record modified2020-04-07
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