Early onset generalized dystonia (DYT1), a movement disorder characterized by involuntary movements and prolonged muscle contraction that result in twisting body motions, tremor, and abnormal posture, has been linked to two mutations (deltaE302 and deltaF323-Y328) in the protein torsinA. Using yeast-two hybrid screens, a novel protein interactor of torsinA, termed printer, has been identified. Printer subcellular and tissue localization will be examined and compared with those of torsinA using confocal microscopy, subcellular fractionation, western blot, and northern blot. The interaction between torsinA and printer will be examined using co-immunoprecipitation, and in vitro binding assay. To test the hypothesis that printer may play a role in the regulation of known and suspected torsinA functions will be examined using in vitro chaperone, ATPase and binding assays. The proposed examination of printer, its interaction with torsinA, and its effect on known torsinA functions may shed light on how torsinA functions are regulated, how this regulation is disturbed by dystonia-related mutations, and may provide a novel therapeutic target for dystonia treatment. ? ?
| Giles, Lisa M; Li, Lian; Chin, Lih-Shen (2009) Printor, a novel torsinA-interacting protein implicated in dystonia pathogenesis. J Biol Chem 284:21765-75 |
| Giles, Lisa M; Li, Lian; Chin, Lih-Shen (2009) TorsinA protein degradation and autophagy in DYT1 dystonia. Autophagy 5:82-4 |
| Giles, Lisa M; Chen, Jue; Li, Lian et al. (2008) Dystonia-associated mutations cause premature degradation of torsinA protein and cell-type-specific mislocalization to the nuclear envelope. Hum Mol Genet 17:2712-22 |
