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Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription.

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

Pubmed ID: 10973986


  • Wood JD
  • Nucifora FC
  • Duan K
  • Zhang C
  • Wang J
  • Kim Y
  • Schilling G
  • Sacchi N
  • Liu JM
  • Ross CA


The Journal of cell biology

Publication Data

September 4, 2000

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS16375
  • Agency: NINDS NIH HHS, Id: NS34172
  • Agency: NINDS NIH HHS, Id: NS38144

Mesh Terms

  • Animals
  • Atrophy
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Globus Pallidus
  • Histone Deacetylases
  • Humans
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Nuclear Matrix
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured