ArticleCells2019
The Ubiquitin Proteasome System Is a Key Regulator of Pluripotent Stem Cell Survival and Motor Neuron Differentiation.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- VEGFAngiogenesis · 2026Article
- Robotic handling preserves iPSC-derived vascular smooth muscle cell differentiation.Materials today. Bio · 2026Article
- Benchmarking In-Cell Proteomics for Profiling Neuroblastoma Cell Differentiation and the Ubiquitin-Proteasome System.Journal of proteome research · 2025Article
- Metformin Protects Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons from Oxidative Damage Through Antioxidant Mechanisms.Neurotoxicity research · 2025Article
- Interactions Between the Ubiquitin-Proteasome System, Nrf2, and the Cannabinoidome as Protective Strategies to Combat Neurodegeneration: Review on Experimental Evidence.Neurotoxicity research · 2024Review
- Ubiquitination contributes to the regulation of GDP-mannose pyrophosphorylase B activity.Frontiers in molecular neuroscience · 2024Article
- Article
- ALS-linked CCNF variant disrupts motor neuron ubiquitin homeostasis.Human molecular genetics · 2023Article
- Proteasome inhibitor MG132 enhances the sensitivity of human OSCC cells to cisplatin via a ROS/DNA damage/p53 axis.Experimental and therapeutic medicine · 2023Article
- Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update.Stem cell research & therapy · 2022Review
- Gel-like inclusions of C-terminal fragments of TDP-43 sequester stalled proteasomes in neurons.EMBO reports · 2022Article
- Progress and challenges in directing the differentiation of human iPSCs into spinal motor neurons.Frontiers in cell and developmental biology · 2022Review
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Genomic and evolutionary classification of lung cancer in never smokers.Nature genetics · 2021Article
- Role of EphA4 in Mediating Motor Neuron Death in MND.International journal of molecular sciences · 2021Review
- Automated in vivo drug screen in zebrafish identifies synapse-stabilising drugs with relevance to spinal muscular atrophy.Disease models & mechanisms · 2021Article
- The Ubiquitin Proteasome System and Skin Fibrosis.Molecular diagnosis & therapy · 2021Review
- Unbiased Label-Free Quantitative Proteomics of Cells Expressing Amyotrophic Lateral Sclerosis (ALS) Mutations inFrontiers in molecular neuroscience · 2021Article
- Genomic Portrait of a Sporadic Amyotrophic Lateral Sclerosis Case in a Large Spinocerebellar Ataxia Type 1 Family.Journal of personalized medicine · 2020Article
- Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin proteasome system (UPS) plays an important role in regulating numerous cellular processes, and a dysfunctional UPS is thought to contribute to motor neuron disease. Consequently, we sought to map the changing ubiquitome in human iPSCs during their pluripotent stage and following differentiation to motor neurons. Ubiquitinomics analysis identified that spliceosomal and ribosomal proteins were more ubiquitylated in pluripotent stem cells, whilst proteins involved in fatty acid metabolism and the cytoskeleton were specifically ubiquitylated in the motor neurons. The UPS regulator, ubiquitin-like modifier activating enzyme 1 (UBA1), was increased 36-fold in the ubiquitome of motor neurons compared to pluripotent stem cells. Thus, we further investigated the functional consequences of inhibiting the UPS and UBA1 on motor neurons. The proteasome inhibitor MG132, or the UBA1-specific inhibitor PYR41, significantly decreased the viability of motor neurons. Consistent with a role of the UPS in maintaining the cytoskeleton and regulating motor neuron differentiation, UBA1 inhibition also reduced neurite length. Pluripotent stem cells were extremely sensitive to MG132, showing toxicity at nanomolar concentrations. The motor neurons were more resilient to MG132 than pluripotent stem cells but demonstrated higher sensitivity than fibroblasts. Together, this data highlights the important regulatory role of the UPS in pluripotent stem cell survival and motor neuron differentiation.
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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.