Atrophin-1, the Dentato-Rubral and Pallido-Luysian Atrophy Gene Product, Interacts with Eto/Mtg8 in the Nuclear Matrix and Represses Transcription

摘要: Dentato-rubral and pallido-luysian atrophy (DRPLA) is one of the family neurodegenerative diseases caused by expansion a polyglutamine tract. The drpla gene product, atrophin-1, widely expressed, has no known function or activity, found in both nuclear cytoplasmic compartments neurons. Truncated fragments atrophin-1 accumulate neuronal nuclei transgenic mouse model DRPLA, may underlie disease phenotype. Using yeast two-hybrid system, we identified ETO/MTG8, component receptor corepressor complexes, as an atrophin-1–interacting protein. When cotransfected into Neuro-2a cells, ETO/MTG8 colocalize discrete structures that contain endogenous mSin3A histone deacetylases. These are sodium dodecyl sulfate–soluble associated with matrix. Cotransfection recruits to matrix, while cofractionate matrix preparations from brains DRPLA mice. Furthermore, cell transfection–based assay, represses transcription. Together, these results suggest associates complexes involved transcriptional regulation. Emerging links between disease-associated proteins, receptors, translocation-leukemia have important repercussions for pathobiology this disorders.