Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone

David L. Stenoien, Chris J. Cummings, Henry P. Adams, Maureen G. Mancini, Kavita Patel, George N. Demartino, Marco Marcelli, Nancy L. Weigel, Michael A. Mancini

Research output: Contribution to journalArticle

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Abstract

Spinal bulbar muscular atrophy is a neurodegenerative disorder caused by a polyglutamine expansion in the androgen receptor (AR). We show in transiently transfected HeLa cells that an AR containing 48 glutamines (ARQ48) accumulates in a hormone-dependent manner in both cytoplasmic and nuclear aggregates. Electron microscopy reveals both types of aggregates to have a similar ultrastructure. ARQ48 aggregates sequester mitochondria and steroid receptor coactivator 1 and stain positively for NEDD8, Hsp70, Hsp90 and HDJ-2/HSDJ. Co-expression of HDJ-2/HSDJ significantly represses aggregate formation. ARQ48 aggregates also label with antibodies recognizing the PA700 proteasome caps but not 20S core particles. These results suggest that ARQ48 accumulates due to protein misfolding and a breakdown in proteolytic processing. Furthermore, the homeostatic disturbances associated with aggregate formation may affect normal cell function.

Original languageEnglish (US)
Pages (from-to)731-741
Number of pages11
JournalHuman Molecular Genetics
Volume8
Issue number5
StatePublished - 1999

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Androgen Receptors
Proteasome Endopeptidase Complex
Heat-Shock Proteins
Nuclear Receptor Coactivator 1
Atrophic Muscular Disorders
Glutamine
HeLa Cells
Neurodegenerative Diseases
Electron Microscopy
Mitochondria
Coloring Agents
Hormones
Antibodies
Proteins
polyglutamine

ASJC Scopus subject areas

  • Genetics

Cite this

Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. / Stenoien, David L.; Cummings, Chris J.; Adams, Henry P.; Mancini, Maureen G.; Patel, Kavita; Demartino, George N.; Marcelli, Marco; Weigel, Nancy L.; Mancini, Michael A.

In: Human Molecular Genetics, Vol. 8, No. 5, 1999, p. 731-741.

Research output: Contribution to journalArticle

Stenoien, DL, Cummings, CJ, Adams, HP, Mancini, MG, Patel, K, Demartino, GN, Marcelli, M, Weigel, NL & Mancini, MA 1999, 'Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone', Human Molecular Genetics, vol. 8, no. 5, pp. 731-741.
Stenoien, David L. ; Cummings, Chris J. ; Adams, Henry P. ; Mancini, Maureen G. ; Patel, Kavita ; Demartino, George N. ; Marcelli, Marco ; Weigel, Nancy L. ; Mancini, Michael A. / Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. In: Human Molecular Genetics. 1999 ; Vol. 8, No. 5. pp. 731-741.
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