PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival

A novel gene, designated PQBP-1, which encodes a 265 residue protein, that binds to the polyglutamine tract of the brain-specific transcription factor Brn-2, was identified. PQBP-1, which also interacts with the polyglutamine tract of triplet repeat disease gene products, binds with a higher affinit y to an expanded polyglutamine tract. PQBP-1 has several functional domains , including hepta- and di-amino acid repeat sequences rich in polar residue s essential for its interaction with the polyglutamine tract, a WWP/WW doma in which binds to proline-rich motifs in other proteins, a putative nuclear localization signal sequence and a C-2 domain implicated in Ca2+-dependent phospholipid signaling. PQBP-1 is located in the nucleus and inhibits tran scriptional activation by Brn-2. Overexpression of PQBP-1 in P19 embryonic carcinoma cells suppresses their growth rate and enhances their susceptibil ity to various stresses including serum deprivation, retinoic acid treatmen t and UV irradiation, Northern blot and in situ hybridization analyses reve aled that PQBP-1 is a ubiquitous protein and is expressed primarily in neur ons throughout the brain, with abundant levels in hippocampus, cerebellar c ortex and olfactory bulb. These results suggest that PQBP-1 mediates import ant cellular functions under physiological and pathological conditions via its interaction with polyglutamine tracts.