ArticleThe Journal of biological chemistry2013
The MID1 E3 ligase catalyzes the polyubiquitination of Alpha4 (α4), a regulatory subunit of protein phosphatase 2A (PP2A): novel insights into MID1-mediated regulation of PP2A.
Article in The Journal of biological chemistry, 2013. 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, 32 citations in OpenAlex.
- Salivary gland transcriptomic analysis and immunophenotyping in the IL-14α transgenic mouse model of Sjögren's disease.Frontiers in dental medicine · 2025Article
- Ubiquitin E3 ligase MID1 inhibits the innate immune response by ubiquitinating IRF3.Immunology · 2021Article
- MID1 and MID2 regulate cell migration and epithelial-mesenchymal transition via modulating Wnt/β-catenin signaling.Annals of translational medicine · 2020Article
- SIRT3, PP2A and TTP protein stability in the presence of TNF-α on vincristine-induced apoptosis of leukaemia cells.Journal of cellular and molecular medicine · 2020Article
- How to Inactivate Human Ubiquitin E3 Ligases by Mutation.Frontiers in cell and developmental biology · 2020Review
- Differential Expression of Genes for Ubiquitin Ligases in Medulloblastoma Subtypes.Cerebellum (London, England) · 2019Article
- Emerging Roles of the TRIM E3 Ubiquitin Ligases MID1 and MID2 in Cytokinesis.Frontiers in physiology · 2019Review
- α4 Coordinates Small Intestinal Epithelium Homeostasis by Regulating Stability of HuR.Molecular and cellular biology · 2018Article
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- The X-Linked-Intellectual-Disability-Associated Ubiquitin Ligase Mid2 Interacts with Astrin and Regulates Astrin Levels to Promote Cell Division.Cell reports · 2016Article
- Molecular dissection of a rice microtubule-associated RING finger protein and its potential role in salt tolerance in Arabidopsis.Plant molecular biology · 2015Article
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- Intellectual disability and autism spectrum disorders: causal genes and molecular mechanisms.Neuroscience and biobehavioral reviews · 2014Review
- Interaction between salt-inducible kinase 2 and protein phosphatase 2A regulates the activity of calcium/calmodulin-dependent protein kinase I and protein phosphatase methylesterase-1.The Journal of biological chemistry · 2014Article
- Identification of sexually dimorphic genes in the neonatal mouse cortex and hippocampus.Brain research · 2014Article
- Predicting targeted drug combinations based on Pareto optimal patterns of coexpression network connectivity.Genome medicine · 2014Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Alpha4 (α4) is a key regulator of protein phosphatase 2A (PP2A) and mTOR in steps essential for cell-cycle progression. α4 forms a complex with PP2A and MID1, a microtubule-associated ubiquitin E3 ligase that facilitates MID1-dependent regulation of PP2A and the dephosphorylation of MID1 by PP2A. Ectopic overexpression of α4 is associated with hepatocellular carcinomas, breast cancer, and invasive adenocarcinomas. Here, we provide data suggesting that α4 is regulated by ubiquitin-dependent degradation mediated by MID1. In cells stably expressing a dominant-negative form of MID1, significantly elevated levels of α4 were observed. Treatment of cells with the specific proteasome inhibitor, lactacystin, resulted in a 3-fold increase in α4 in control cells and a similar level in mutant cells. Using in vitro assays, individual MID1 E3 domains facilitated monoubiquitination of α4, whereas full-length MID1 as well as RING-Bbox1 and RING-Bbox1-Bbox2 constructs catalyzed its polyubiquitination. In a novel non-biased functional screen, we identified a leucine to glutamine substitution at position 146 within Bbox1 that abolished MID1-α4 interaction and the subsequent polyubiquitination of α4, indicating that direct binding to Bbox1 was necessary for the polyubiquitination of α4. The mutant had little impact on the RING E3 ligase functionality of MID1. Mass spectrometry data confirmed Western blot analysis that ubiquitination of α4 occurs only within the last 105 amino acids. These novel findings identify a new role for MID1 and a mechanism of regulation of α4 that is likely to impact the stability and activity level of PP2Ac.
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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.