Identification of the full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor

Neurodegeneration in Huntington's disease (HD) is associated with an elonga ted glutamine tract in the widely expressed huntingtin protein. Although th e pathogenic mechanisms are still unknown, the distinct physical properties of mutant huntingtin in the brain suggest that other factors including hun tingtin-interacting proteins might play a specific role. We have previously identified a DNA-binding motif in the proximal E1A promoter of adenovirus serotype 12 as responsible for E1A autoregulation. Here, we identified the p231HBP protein as a DNA-binding factor, the C-terminal portion of which ha s recently been characterized as the huntingtin-interacting protein HYPB of unknown function. We have determined the full-length cDNA sequence, identi fied several domains supporting its gene regulatory functions, and mapped t he HBP231 gene to chromosome 3p21.2-p21.3. Our results provide an interesti ng molecular link between huntingtin and a DNA-binding factor, implicating that this interaction might result in the alteration of cellular gene expre ssion involved in HD pathogenesis.