Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death.

PQBP-1 was isolated on the basis of its interaction with polyglutamine tracts. In this study, using in vitro and in vivo assays, we show that the association between ataxin-1 and PQBP-1 is positively influenced by expanded polyglutamine sequences. In cell lines, interaction between the two molecules induces apoptotic cell death. As a possible mechanism underlying this phenomenon, we found that mutant ataxin-1 enhances binding of PQBP-1 to the C-terminal domain of RNA polymerase II large subunit (Pol II). This reduces the level of phosphorylated Pol II and transcription. Our results suggest the involvement of PQBP-1 in the pathology of spinocerebellar ataxia type 1 (SCA1) and support the idea that modified transcription underlies polyglutamine-mediated pathology.

Pubmed ID: 12062018 RIS Download

Mesh terms: Aged | Animals | Ataxin-1 | Ataxins | Carrier Proteins | Cell Death | Cell Nucleus | Cell Survival | Cells, Cultured | Cerebellum | Disease Models, Animal | Female | Genes, Regulator | Humans | Inclusion Bodies | Macromolecular Substances | Mice | Nerve Tissue Proteins | Neurons | Nuclear Proteins | Peptides | Protein Structure, Tertiary | RNA Polymerase II | Spinocerebellar Ataxias | Trinucleotide Repeat Expansion