ArticleThe Journal of biological chemistry2008
The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit Bbeta2 antagonizes neuronal survival by promoting mitochondrial fission.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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.
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Who cites it
44 citing papers in PubMed, 87 citations in OpenAlex.
- Abnormal Amyloidogenesis Identified in Plasma of Patients with Spinocerebellar Ataxia Type 12.Cerebellum (London, England) · 2026Article
- A multiomics Mendelian randomization study on PANoptosis-related genes and gastric cancer risk.The Journal of international medical research · 2026Article
- A distinct PP2A subunit regulates local protein phosphorylation at the axon initial segment.Nature communications · 2025Article
- PPP2/PP2A-mediated dephosphorylation of LC3B links PINK1-PRKN/Parkin-mediated mitophagy to SCA12 pathogenesis.Autophagy · 2025Article
- The Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.Aging and disease · 2025Review
- De novo missense variants in the PP2A regulatory subunit PPP2R2B in a neurodevelopmental syndrome: potential links to mitochondrial dynamics and spinocerebellar ataxias.Human molecular genetics · 2025Article
- Microcystin-LR, a Cyanobacterial Toxin, Induces Changes in the Organization of Membrane Compartments in Arabidopsis.Microorganisms · 2023Article
- Protein phosphatase 2A - structure, function and role in neurodevelopmental disorders.Journal of cell science · 2021Review
- Review
- Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease.Frontiers in endocrinology · 2021Review
- Cells of the adult human heart.Nature · 2020Article
- Protein phosphatase 2A B55β limits CD8+ T cell lifespan following cytokine withdrawal.The Journal of clinical investigation · 2020Article
- Deletion of a Neuronal Drp1 Activator Protects against Cerebral Ischemia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- MitochondrialThe Journal of biological chemistry · 2017Article
- Mitochondrial dynamics in neuronal injury, development and plasticity.Journal of cell science · 2017Review
- Article
- Phosphatase 2A Inhibition Affects Endoplasmic Reticulum and Mitochondria Homeostasis Via Cytoskeletal Alterations in Brain Endothelial Cells.Molecular neurobiology · 2017Article
- Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons.Cell death and differentiation · 2016Article
- Protein phosphatase 2A plays an important role in migration of bone marrow stroma cells.Molecular and cellular biochemistry · 2016Article
- Neuropathology and Cellular Pathogenesis of Spinocerebellar Ataxia Type 12.Movement disorders : official journal of the Movement Disorder Society · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The neurodegenerative disorder spinocerebellar ataxia 12 (SCA12) is caused by CAG repeat expansion in the non-coding region of the PPP2R2B gene. PPP2R2B encodes Bbeta1 and Bbeta2, alternatively spliced and neuron-specific regulatory subunits of the protein phosphatase 2A (PP2A) holoenzyme. We show here that in PC12 cells and hippocampal neurons, cell stressors induced a rapid translocation of PP2A/Bbeta2 to mitochondria to promote apoptosis. Conversely, silencing of PP2A/Bbeta2 protected hippocampal neurons against free radical-mediated, excitotoxic, and ischemic insults. Evidence is accumulating that the mitochondrial fission/fusion equilibrium is an important determinant of cell survival. Accordingly, we found that Bbeta2 expression induces mitochondrial fragmentation, whereas Bbeta2 silencing or inhibition resulted in mitochondrial elongation. Based on epistasis experiments involving Bcl2 and core components of the mitochondrial fission machinery (Fis1 and dynamin-related protein 1), mitochondrial fragmentation occurs upstream of apoptosis and is both necessary and sufficient for hippocampal neuron death. Our data provide the first example of a proapoptotic phosphatase that predisposes to neuronal death by promoting mitochondrial division and point to a possible imbalance of the mitochondrial morphogenetic equilibrium in the pathogenesis of SCA12.
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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.