Degradation properties of polyglutamine-expanded human androgen receptor in transfected cells.
Spinal and bulbar muscular atrophy is an inherited motor neuronopathy caused by the expansion of a polyglutamine sequence in the androgen receptor. Recent evidence suggests that the presence of a long polyglutamine stretch may impair the regulation of the steady-state levels of disease-causing proteins. We compared the degradation characteristics of androgen receptors with 20 or 51 glutamine residues in transfected HEK293 cells. Both forms accumulated after treatment with lactacystin, demonstrating degradation by the ubiquitin-proteasome pathway. The half-life of the two forms of the androgen receptor was approximately 6 h, as determined by cycloheximide chase. These results suggest that the presence of an expanded polyglutamine sequence does not influence degradation rates directly and that differential regulation of steady-state levels of the androgen receptor in neurons would require neuron-specific, polyglutamine-dependent, factors.
Department of Neurology, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
Daniel A
DA
Cullen
P Nigel
PN
Leigh
Jean-Marc
JM
Gallo
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007668:Kidney; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011944:Receptors, Androgen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods
D000900:Anti-Bacterial Agents; D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; D011500:Protein Synthesis Inhibitors; D011944:Receptors, Androgen; C067713:lactacystin; C097188:polyglutamine; D003513:Cycloheximide; D004318:Doxycycline; D000111:Acetylcysteine