ArticleThe Journal of biological chemistry2019
Changes in protein function underlie the disease spectrum in patients with CHIP mutations.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Domain-dependent uncoupling of the co-chaperone and E3 ubiquitin ligase CHIP underlies heterogeneity in spinocerebellar ataxia 48.The Journal of biological chemistry · 2026Article
- A novel STUB1 p.(Gln118*) nonsense variant in compound heterozygosity causes autosomal recessive spinocerebellar ataxia type 16 in a Chinese patient.BMC neurology · 2026Article
- Mucus polymer concentration andmBio · 2024Article
- Die Hard: Necroptosis and its Impact on Age-Dependent Neuroinflammatory Diseases.Frontiers in cell death · 2024Article
- The molecular basis of spinocerebellar ataxia type 48 caused by a de novo mutation in the ubiquitin ligase CHIP.The Journal of biological chemistry · 2022Article
- Chemical Regulation of the Protein Quality Control E3 Ubiquitin Ligase C-Terminus of Hsc70 Interacting Protein (CHIP).Chembiochem : a European journal of chemical biology · 2022Article
- A Severe Dementia Syndrome Caused by Intron Retention and Cryptic Splice Site Activation inFrontiers in molecular neuroscience · 2022Article
- Review
- Clinical and functional characterization of a novel STUB1 frameshift mutation in autosomal dominant spinocerebellar ataxia type 48 (SCA48).Journal of biomedical science · 2021Article
- Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia.Journal of neurology · 2021Article
- C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside.Current neuropharmacology · 2021Review
- Chip Protein U-Box Domain Truncation Affects Purkinje Neuron Morphology and Leads to Behavioral Changes in Zebrafish.Frontiers in molecular neuroscience · 2021Article
- Clinical, neuropathological, and genetic characterization of STUB1 variants in cerebellar ataxias: a frequent cause of predominant cognitive impairment.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- CHIP mutations affect the heat shock response differently in human fibroblasts and iPSC-derived neurons.Disease models & mechanisms · 2020Article
- CHIP as a therapeutic target for neurological diseases.Cell death & disease · 2020Review
- Spinocerebellar ataxia type 48: last but not least.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- Clinical and Genetic Characterization of Autosomal Recessive Spinocerebellar Ataxia Type 16 (SCAR16) in Taiwan.Cerebellum (London, England) · 2020Article
- Clinical and pathologic phenotype of a large family with heterozygousNeurology. Genetics · 2020Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Monogenetic disorders that cause cerebellar ataxia are characterized by defects in gait and atrophy of the cerebellum; however, patients often suffer from a spectrum of disease, complicating treatment options. Spinocerebellar ataxia autosomal recessive 16 (SCAR16) is caused by coding mutations in STUB1, a gene that encodes the multifunctional enzyme CHIP (C terminus of HSC70-interacting protein). The disease spectrum of SCAR16 includes a varying age of disease onset, cognitive dysfunction, increased tendon reflex, and hypogonadism. Although SCAR16 mutations span the multiple functional domains of CHIP, it is unclear whether the location of the mutation and the change in the biochemical properties of CHIP contributes to the clinical spectrum of SCAR16. In this study, we examined relationships between the clinical phenotypes of SCAR16 patients and the changes in biophysical, biochemical, and functional properties of the corresponding mutated protein. We found that the severity of ataxia did not correlate with age of onset; however, cognitive dysfunction, increased tendon reflex, and ancestry were able to predict 54% of the variation in ataxia severity. We further identified domain-specific relationships between biochemical changes in CHIP and clinical phenotypes and specific biochemical activities that associate selectively with either increased tendon reflex or cognitive dysfunction, suggesting that specific changes to CHIP-HSC70 dynamics contribute to the clinical spectrum of SCAR16. Finally, linear models of SCAR16 as a function of the biochemical properties of CHIP support the concept that further inhibiting mutant CHIP activity lessens disease severity and may be useful in the design of patient-specific targeted approaches to treat SCAR16.
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