ArticlePloS one2013
Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- The ubiquitin-proteasome system and proteostasis in the cochlea and sensorineural hearing disorders.Molecular biomedicine · 2026Review
- Proteostasis and ageing dissidence.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Ubiquitination plays a key role in an insecticide resistance fitness cost.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lycorine hydrochloride directly targets UBA1 to suppress cellular senescence.Acta pharmaceutica Sinica. B · 2025Article
- A set of common buccal CpGs that predict epigenetic age and associate with lifespan-regulating genes.iScience · 2022Article
- X-Linked Spinal Muscular Atrophy 2 due to a Synonymous Variant in theMolecular syndromology · 2022Article
- Ubiquitin-proteasome pathway annotation inGigaByte (Hong Kong, China) · 2022Article
- A novel Xp11.22-22.33 deletion suggesting a possible mechanism of congenital cervical spinal muscular atrophy.Molecular genetics & genomic medicine · 2021Article
- Unstructured Biology of Proteins from Ubiquitin-Proteasome System: Roles in Cancer and Neurodegenerative Diseases.Biomolecules · 2020Article
- Genetic Pathways of Aging and Their Relevance in the Dog as a Natural Model of Human Aging.Frontiers in genetics · 2019Review
- The role of survival motor neuron protein (SMN) in protein homeostasis.Cellular and molecular life sciences : CMLS · 2018Review
- The Good, the Bad, and the Ugly of ROS: New Insights on Aging and Aging-Related Diseases from Eukaryotic and Prokaryotic Model Organisms.Oxidative medicine and cellular longevity · 2018Review
- Molecular Basis for K63-Linked Ubiquitination Processes in Double-Strand DNA Break Repair: A Focus on Kinetics and Dynamics.Journal of molecular biology · 2017Review
- Proteostasis and ageing: insights from long-lived mutant mice.The Journal of physiology · 2017Review
- Co-expression Patterns betweenFrontiers in molecular neuroscience · 2017Article
- Article
- UBA1: At the Crossroads of Ubiquitin Homeostasis and Neurodegeneration.Trends in molecular medicine · 2015Review
- Roles of ubiquitination and SUMOylation on prostate cancer: mechanisms and clinical implications.International journal of molecular sciences · 2015Review
- Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies.Brain : a journal of neurology · 2014Review
- Ubiquitin sets the timer: impacts on aging and longevity.Nature structural & molecular biology · 2014Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Neurodegenerative diseases cause tremendous suffering for those afflicted and their families. Many of these diseases involve accumulation of mis-folded or aggregated proteins thought to play a causal role in disease pathology. Ubiquitinated proteins are often found in these protein aggregates, and the aggregates themselves have been shown to inhibit the activity of the proteasome. These and other alterations in the Ubiquitin Pathway observed in neurodegenerative diseases have led to the question of whether impairment of the Ubiquitin Pathway on its own can increase mortality or if ongoing neurodegeneration alters Ubiquitin Pathway function as a side-effect. To address the role of the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reached adulthood. These mutants exhibited further reduced lifespan and showed inappropriate Ras activation in the brain. Removing just one functional copy of Ras restored the lifespan of heterozygous E1 mutants to that of wild-type flies and increased the survival of homozygous E1 mutants. E1 homozygous mutants also showed severe motor impairment. Our findings suggest that processes that impair the Ubiquitin Pathway are sufficient to cause early mortality. Reduced lifespan and motor impairment are seen in the human disease X-linked Infantile Spinal Muscular Atrophy, which is associated with mutation in human E1 warranting further analysis of these mutants as a potential animal model for study of this disease.
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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.