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Huntingtin interacting protein 14 (HIP14, ZDHHC17) is a huntingtin (HTT) interacting protein with palmitoyl transferase activity. In order to interrogate the function of Hip14, we generated mice with disruption in their Hip14 gene. Hip14-/- mice displayed behavioral, biochemical and neuropathological defects that are reminiscent of Huntington disease (HD). Palmitoylation of other HIP14 substrates, but not Htt, was reduced in the Hip14-/- mice. Hip14 is dysfunctional in the presence of mutant htt in the YAC128 mouse model of HD, suggesting that altered palmitoylation mediated by HIP14 may contribute to HD.

Original publication

DOI

10.1093/hmg/ddr308

Type

Journal article

Journal

Hum Mol Genet

Publication Date

15/10/2011

Volume

20

Pages

3899 - 3909

Keywords

Acyltransferases, Animals, Cell Death, Corpus Striatum, Disease Models, Animal, Dopamine and cAMP-Regulated Phosphoprotein 32, Enkephalins, Huntington Disease, Lipoylation, Mice, Mice, Knockout, Motor Activity, Mutant Proteins, Nerve Tissue Proteins, Neurons, Serotonin Plasma Membrane Transport Proteins, Synapses