Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death. 1206 12

A body of experimental evidence indicates that transcription and/or mRNA processing factors interacting with the polyglutamine disease gene products play crucial roles in the pathology. PQBP-1 is one of these factors and it has been shown to interact with the spinocerebellar ataxia type-1 (SCA1) disease gene product, ataxin-1. Our previous data suggested that relatively high expression of PQBP-1 in the cerebellum might explain the selective neuronal degeneration of SCA1. To further test whether PQBP-1 expression level regulates neuronal death, we generated transgenic mice of human PQBP-1 driven by a regulatory element for ubiquitous gene expression. The mice showed a late-onset and gradually progressive motor neuron disease-like phenotype, which might be related to neurogenic muscular atrophy observed in SCA1 patients. Ataxia could not be discriminated from predominant progressive weakness. Pathological examinations of the transgenic mice revealed loss of Purkinje and granular cells in the cerebellum as well as that of spinal motor neurons, corresponding to the pathology of human SCA1. These findings show that excessive action of PQBP-1 causes neuronal dysfunction and support PQBP-1 being involved in the pathology of SCA1.
 ...
PMID:PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype. 1265 67