ArticleJournal of virology2012
Transformation by E1A oncoprotein involves ubiquitin-mediated proteolysis of the neuronal and tumor repressor REST in the nucleus.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Regulation of Glutathione Peroxidase 4 in Diabetic Retinopathy.International journal of molecular sciences · 2026Article
- Review
- REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer.Medicina (Kaunas, Lithuania) · 2023Article
- Neuroendocrine Key Regulator Gene Expression in Merkel Cell Carcinoma.Neoplasia (New York, N.Y.) · 2018Article
- Review
- Preventing P-gp Ubiquitination Lowers Aβ Brain Levels in an Alzheimer's Disease Mouse Model.Frontiers in aging neuroscience · 2018Article
- Modulation of nuclear REST by alternative splicing: a potential therapeutic target for Huntington's disease.Journal of cellular and molecular medicine · 2017Article
- Dissecting the Molecular Pathway Involved in PLK2 Kinase-mediated α-Synuclein-selective Autophagic Degradation.The Journal of biological chemistry · 2017Article
- Article
- Ubiquitin-activating enzyme activity contributes to differential accumulation of mutant huntingtin in brain and peripheral tissues.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Posttranslational modification of mitochondrial transcription factor A in impaired mitochondria biogenesis: implications in diabetic retinopathy and metabolic memory phenomenon.Experimental eye research · 2014Article
- The deubiquitylase USP15 stabilizes newly synthesized REST and rescues its expression at mitotic exit.Cell cycle (Georgetown, Tex.) · 2013Article
- Ras Participates in the Regulation of the Stability of Adenoviral Protein E1A via MAP-kinase ERK.Acta naturaeArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The adenovirus early region 1A (E1A) protein promotes cell immortalization and transformation by mediating the activities of key cellular regulators. The repressor element 1-silencing transcription factor (REST), which is a major neuronal and tumor suppressor, was previously found mainly in the cytoplasm rather than in the nuclei of adenovirus-transformed rodent cells (22). We now demonstrate that the loss of REST in the nucleus is due to its rapid degradation by the ubiquitin-proteasome system. Only nuclear REST, but not its cytoplasmic counterpart, was ubiquitinated and degraded. REST degradation was blocked by the ubiquitination inhibitor PYR-41 and the proteasome inhibitor MG-132 but not by the nuclear export inhibitor leptomycin B. REST degradation required both of its two C-terminal degrons that are recognized by the ubiquitin ligase SCF(β-TrCP), since deletion or mutation of either degron eliminated degradation. Importantly, E1A was shown to mediate REST ubiquitination and degradation by upregulating β-TrCP. Knockdown of E1A in virus-transformed cells reduced both β-TrCP and ubiquitination of nuclear REST. In contrast, when expressed in HeLa cells, E1A enhanced the degradation of nuclear REST. Reconstitution of REST in virus-transformed cells negatively affected E1A-mediated cell proliferation and anchorage-independent growth. These data strongly indicate that E1A stimulates ubiquitination and proteolysis of REST in the nucleus, thereby abolishing the tumor suppressor functions of REST.
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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.