Polyglutamine neurodegenerative diseases and regulation of transcription: assembling the puzzle.
The polyglutamine disorders are a class of nine neuro-degenerative disorders that are inherited gain-of-function diseases caused by expansion of a translated CAG repeat. Even though the disease-causing proteins are widely expressed, specific collections of neurons are more susceptible in each disease, resulting in characteristic patterns of pathology and clinical symptoms. One hypothesis poses that altered protein function is fundamental to pathogenesis, with protein context of the expanded polyglutamine having key roles in disease-specific processes. This review will focus on the role of the disease-causing polyglutamine proteins in gene transcription and the extent to which the mutant proteins induce disruption of transcription.
Riley
Brigit E
BE
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Orr
Harry T
HT
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D019680:Trinucleotide Repeat Expansion
D004268:DNA-Binding Proteins; D010455:Peptides; D014157:Transcription Factors; C097188:polyglutamine