Huntingtin Interacting Protein K (HYPK)

Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat encoding an N-terminal polyglutamine region in huntingtin (HTT) to more than 34 units.

HYPK interacted with the isolated N-terminal region of human huntingtin containing either 16 (H16) or 40 (H40) glutamines. Coexpression of HYPK reduced H40 aggregate formation and H40-induced apoptosis. Purified recombinant HYPK showed chaperone-like activity in vitro against temperature-induced protein aggregates and in vivo against heat-denatured proteins. In cells expressing HYPK and H40, the chaperone-like activity of HYPK against other protein substrates was reduced compared with cells expressing HYPK and H16, apparently due to interaction of HYPK with H40 protein aggregates.