ArticleHuman molecular genetics2009
The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 193 citations in OpenAlex.
- The isolated HEPN domain of SACSIN exhibits RNA-binding activity.Cellular and molecular life sciences : CMLS · 2026Article
- Duplication of 4-bp in SACS leads to autosomal recessive spastic ataxia of Charlevoix-Saguenay type in two Pakistani patients.Human genome variation · 2026Article
- Coral Genetic Structure in the Western Indian Ocean Mirrors Ocean Circulation and Thermal Stress History.Evolutionary applications · 2026Article
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- Frameshift and Copy Number Variants inNeurology. Genetics · 2025Article
- Charlevoix-Saguenay spastic ataxia: a novel mutation in the SACS gene.Acta neurologica Belgica · 2025Article
- S100B Mitigates Cytoskeletal and Mitochondrial Alterations in a Glial Cell Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.Molecular neurobiology · 2025Article
- Identification of a novel SACS gene mutation leading to spastic ataxia Charlevoix-Saguenay type: a case report.Journal of medical case reports · 2025Article
- Alterations in the NaCerebellum (London, England) · 2025Article
- Genetic analysis of three patients from two unrelated Chinese families with autosomal recessive spastic ataxia of Charlevoix-Saguenay.BMC medical genomics · 2025Article
- Current and future applications of brain magnetic resonance imaging in ARSACS.Cerebellum (London, England) · 2025Review
- ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.Cerebellum (London, England) · 2025Review
- Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Masquerading as Charcot-Marie-Tooth Disease: A Case Study and Literature Review of Korean Patients.Journal of movement disorders · 2025Article
- Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin.International journal of molecular sciences · 2024Article
- The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias.Cerebellum (London, England) · 2024Review
- Investigating the genetic basis of hereditary spastic paraplegia and cerebellar Ataxia in Pakistani families.BMC neurology · 2024Article
- Gene expression response under thermal stress in two Hawaiian corals is dominated by ploidy and genotype.Ecology and evolution · 2024Article
- Article
- Compound Heterozygous Mutations ofInternational journal of molecular sciences · 2024Article
- Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
An extensive protein-protein interaction network has been identified between proteins implicated in inherited ataxias. The protein sacsin, which is mutated in the early-onset neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay, is a node in this interactome. Here, we have established the neuronal expression of sacsin and functionally characterized domains of the 4579 amino acid protein. Sacsin is most highly expressed in large neurons, particularly within brain motor systems, including cerebellar Purkinje cells. Its subcellular localization in SH-SY5Y neuroblastoma cells was predominantly cytoplasmic with a mitochondrial component. We identified a putative ubiquitin-like (UbL) domain at the N-terminus of sacsin and demonstrated an interaction with the proteasome. Furthermore, sacsin contains a predicted J-domain, the defining feature of DnaJ/Hsp40 proteins. Using a bacterial complementation assay, the sacsin J-domain was demonstrated to be functional. The presence of both UbL and J-domains in sacsin suggests that it may integrate the ubiquitin-proteasome system and Hsp70 function to a specific cellular role. The Hsp70 chaperone machinery is an important component of the cellular response towards aggregation prone mutant proteins that are associated with neurodegenerative diseases. We therefore investigated the effects of siRNA-mediated sacsin knockdown on polyglutamine-expanded ataxin-1. Importantly, SACS siRNA did not affect cell viability with GFP-ataxin-1[30Q], but enhanced the toxicity of GFP-ataxin-1[82Q], suggesting that sacsin is protective against mutant ataxin-1. Thus, sacsin is an ataxia protein and a regulator of the Hsp70 chaperone machinery that is implicated in the processing of other ataxia-linked proteins.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.