Versatile members of the DNAJ family show Hsp70 dependent anti-aggregation activity on RING1 mutant parkin C289G
| Autor: | Kakkar, Vaishali, Kuiper, E F Elsiena, Pandey, Abhinav, Braakman, Ineke, Kampinga, Harm H, Sub Cellular Protein Chemistry, Cellular Protein Chemistry |
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| Přispěvatelé: | Molecular Neuroscience and Ageing Research (MOLAR), Sub Cellular Protein Chemistry, Cellular Protein Chemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ubiquitin-Protein Ligases Protein domain Mutant Nerve Tissue Proteins Protein aggregation Biology DNAJ Protein medicine.disease_cause Article Parkin DISEASE UBIQUITIN 03 medical and health sciences 0302 clinical medicine Protein Domains Ubiquitin Chaperones medicine Humans HSP70 Heat-Shock Proteins Genetics POLYGLUTAMINE PEPTIDES Mutation Multidisciplinary MUTATIONS HEK 293 cells Parkinson Disease HSP40 Heat-Shock Proteins ALPHA-SYNUCLEIN AGGREGATION DISTINCT FUNCTIONS HEK293 Cells 030104 developmental biology Amino Acid Substitution MOLECULAR CHAPERONES AMYLOID FORMATION Proteolysis CELLS biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, 6:34830. Nature Publishing Group Scientific Reports, 6. NLM (Medline) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Parkinson’s disease is one of the most common neurodegenerative disorders and several mutations in different genes have been identified to contribute to the disease. A loss of function parkin RING1 domain mutant (C289G) is associated with autosomal-recessive juvenile-onset Parkinsonism (AR-JP) and displays altered solubility and sequesters into aggregates. Single overexpression of almost each individual member of the Hsp40 (DNAJ) family of chaperones efficiently reduces parkin C289G aggregation and requires interaction with and activity of endogenously expressed Hsp70 s. For DNAJB6 and DNAJB8, potent suppressors of aggregation of polyglutamine proteins for which they rely mainly on an S/T-rich region, it was found that the S/T-rich region was dispensable for suppression of parkin C289G aggregation. Our data implies that different disease-causing proteins pose different challenges to the protein homeostasis system and that DNAJB6 and DNAJB8 are highly versatile members of the DNAJ protein family with multiple partially non-overlapping modes of action with respect to handling disease-causing proteins, making them interesting potential therapeutic targets. |
| Databáze: | OpenAIRE |
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