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Stabilizing the Hsp70-Tau Complex Promotes Turnover in Models of Tauopathy
- Source :
- Cell chemical biology, vol 23, iss 8
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Heat shock protein 70 (Hsp70) is a chaperone that normally scans the proteome and initiates the turnover of some proteins (termed “clients”) by linking them to the degradation pathways. This activity is critical to normal protein homeostasis, yet it appears to fail in diseases associated with abnormal protein accumulation. It is not clear why Hsp70 promotes client degradation under some conditions, while sparing that protein under others. Here, we use a combination of chemical biology and genetics strategies to systematically perturb the affinity of Hsp70 for the model client, tau. This approach revealed that tight complexes between Hsp70 and tau are associated with enhanced turnover while transient interactions favored tau retention. These results suggest that client affinity is one important parameter governing Hsp70-mediated quality control.
- Subjects :
- 0301 basic medicine
Aging
Clinical Biochemistry
Neurodegenerative
Alzheimer's Disease
Biochemistry
0302 clinical medicine
Models
Drug Discovery
Tumor Cells, Cultured
2.1 Biological and endogenous factors
Normal protein
Aetiology
Cultured
Molecular Structure
biology
Protein Stability
Tumor Cells
Cell biology
Tauopathies
Proteome
Thiazolidines
Molecular Medicine
Tauopathy
Drug
Chemical biology
tau Proteins
Models, Biological
Article
Dose-Response Relationship
Structure-Activity Relationship
03 medical and health sciences
Acquired Cognitive Impairment
medicine
Humans
Structure–activity relationship
HSP70 Heat-Shock Proteins
Benzothiazoles
Molecular Biology
Pharmacology
Dose-Response Relationship, Drug
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Biological
medicine.disease
Brain Disorders
Hsp70
030104 developmental biology
Hela Cells
Chaperone (protein)
biology.protein
Dementia
Generic health relevance
030217 neurology & neurosurgery
Homeostasis
HeLa Cells
Subjects
Details
- ISSN :
- 24519456
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Cell Chemical Biology
- Accession number :
- edsair.doi.dedup.....64e38cfa03e80d43361d88f38e0f7265