SUMO Modification of Huntingtin and Huntington's Disease Pathology
Memorial Sloan Kettering Cancer Center · University of Milan · +3 more institutions
Abstract
Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report that a pathogenic fragment of Htt (Httex1p) can be modified either by small ubiquitin-like modifier (SUMO)-1 or by ubiquitin on identical lysine residues. In cultured cells, SUMOylation stabilizes Httex1p, reduces its ability to form aggregates, and promotes its capacity to repress transcription. In a Drosophila model of HD, SUMOylation of Httex1p exacerbates neurodegeneration, whereas ubiquitination of Httex1p abrogates neurodegeneration. Lysine mutations that prevent both SUMOylation and ubiquitination of Httex1p reduce HD pathology,…
Citation impact
- FWCI
- 13.90
- Percentile
- 100%
- References
- 48
Authors
13- JSJoan S. Steffan
Memorial Sloan Kettering Cancer Center, University of Milan, University of California, Irvine, University of California, Irvine Medical Center, Irvine University
- NANamita Agrawal
Memorial Sloan Kettering Cancer Center, University of Milan, University of California, Irvine, University of California, Irvine Medical Center, Irvine University
- JPJudit Pallos
Memorial Sloan Kettering Cancer Center, University of Milan, University of California, Irvine, University of California, Irvine Medical Center, Irvine University
- ERErica Rockabrand
Memorial Sloan Kettering Cancer Center, University of Milan, University of California, Irvine, University of California, Irvine Medical Center, Irvine University
- LCLloyd C. Trotman
Memorial Sloan Kettering Cancer Center, University of Milan, University of California, Irvine, University of California, Irvine Medical Center, Irvine University
Topics & keywords
- SUMO protein
- Huntingtin
- Neurodegeneration
- Ubiquitin
- Lysine
- Huntington's disease
- Cell biology
- Huntingtin Protein