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SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation
- Source :
- Recercat. Dipósit de la Recerca de Catalunya, instname, Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, Cell reports, Cell Reports, Cell Reports; Vol 4, Cell Reports, Vol 4, Iss 2, Pp 362-375 (2013), Recercat: Dipósit de la Recerca de Catalunya, Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya), OâRourke, Jacqueline Gire; Gareau, Jaclyn R.; Ochaba, Joseph; Song, Wan; Raskó, Tamás; Reverter, David; et al.(2013). SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation. Cell Reports, 4(2), 362-375. doi: 10.1016/j.celrep.2013.06.034. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/0ww148xb
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- SUMMARY A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression.
- Subjects :
- Male
Huntingtin
Mutant
SUMO protein
medicine.disease_cause
Gene
environment and public health
Mice
0302 clinical medicine
Catalytic Domain
Medicine and Health Sciences
lcsh:QH301-705.5
Peptide sequence
Aged, 80 and over
Huntingtin Protein
0303 health sciences
Gene knockdown
Mutation
Life Sciences
Interaction Network
Transfection
Protein Inhibitors of Activated STAT
Huntington Disease
Small Ubiquitin-Related Modifier Proteins
Drosophila
Female
Function and Dysfunction of the Nervous System
congenital, hereditary, and neonatal diseases and abnormalities
Ubiquitin-Protein Ligases
Molecular Sequence Data
Activation
Nerve Tissue Proteins
Biology
Repeat
Article
General Biochemistry, Genetics and Molecular Biology
Aggregation
03 medical and health sciences
mental disorders
medicine
Animals
Humans
Amino Acid Sequence
Aged
030304 developmental biology
Conjugation
Sumoylation
Molecular biology
nervous system diseases
Mice, Inbred C57BL
Disease Pathogenesis
enzymes and coenzymes (carbohydrates)
Posttranslational Modifications
lcsh:Biology (General)
nervous system
Mice, Inbred CBA
Protein Processing, Post-Translational
030217 neurology & neurosurgery
HeLa Cells
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....517096cf1e2043fe4d5dc48600a7e7ce