In several neurodegenerative diseases, proteins that bear expanded polyglutamine repeats aggregate, a process that somehow leads to the demise of neurons. Nucifora et al. studied the interaction of aberrant versions of huntingtin (which is affected in Huntington's disease) and atrophin (which is affected in dentatorubral and pallidoluysian atrophy) that contain expanded polyglutamine repeats. These aberrant proteins avidly bound to the transcriptional coactivator CREB-binding protein (CBP) and prevented the transcription of target genes known to be crucial for neuronal survival.
F. C. Nucifora Jr., M. Sasaki, M. F. Peters, H. Huang, J. K. Cooper, M. Yamada, H. Takahashi, S. Tsuji, J. Troncoso, V. L. Dawson, T. M. Dawson, C. A. Ross, Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291, 2423-2428 (2001). [Abstract] [Full Text]