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Neuronal ELAV proteins enhance mRNA stability by a PKCα-dependent pathway
Open accessAbstract
More than 1 in 20 human genes bear in the mRNA 3′ UTR a specific motif called the adenine- and uridine-rich element (ARE), which posttranscriptionally determines its expression in response to cell environmental signals. ELAV (embryonic lethal abnormal vision) proteins are the only known ARE-binding factors that are able to stabilize the bound mRNAs, thereby positively controlling gene expression. Here, we show that in human neuroblastoma SH-SY5Y cells, neuron-specific ELAV (nELAV) proteins (HuB, HuC, and HuD) are up-regulated and redistributed by 15 min of treatment with the activators of PKC phorbol esters and bryostatin-1. PKC stimulation also induces nELAV proteins to colocalize with the translocated PKCα isozyme preferentially on the cytoskeleton, with a concomitant increase of nELAV threonine phosphorylation. The same treatment promotes stabilization of growth-associated protein 43 (GAP-43) mRNA, a well known nELAV target, and induces an early increase in GAP-43 protein concentration, again only in the cytoskeletal cell fraction. Genetic or pharmacological inactivation of PKCα abolishes nELAV protein cytoskeletal up-regulation, GAP-43 mRNA stabilization, and GAP-43 protein increase, demonstrating the primary role of this specific PKC isozyme in the cascade of nELAV recruitment. Finally, in vivo PKC activation is associated with an up-regulation of nELAV proteins in the hippocampal rat brain. These findings suggest a model for gene expression regulation by nELAV proteins through a PKCα-dependent pathway that is relevant for the cellular programs in which ARE-mediated control plays a pivotal role.
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“Moreover, stimulation of PKCα promotes its interaction with nELAV proteins resulting in their phosphorylation at threonine residues, redistribution to the neuronal cytoskeletal and membrane fractions, and stabilization of GAP-43 mRNA.”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Pascale et al. 2005
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“Various conditions, including KCl depolarization of primary hippocampal neurons, cocaine, or seizure treatment of mice and phorbol ester or bryostatin-1 application to human neuroblastoma (NB) cells, result in an augmented abundance of HuD, its redistribution to neurites, and its increased association with mRNAs and mRNP components (Pascale et al. 2005; Tiruchinapalli et al. 2008a,b).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Pascale et al. 2005
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“The classical PKCα isoform was shown to increase nELAV levels and provoke their nuclear export following treatment of SH-SY5Y NB cells with the PKC-activating compounds phorbol esters and bryostatin-1 (Pascale et al. 2005).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Pascale et al. 2005
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Metadata
- Authors
- Pascale, A., Amadio, M., Scapagnini, G., Lanni, C., Racchi, M., Provenzani, A., Govoni, S., Alkon, D. L., & Quattrone, A.
- Affiliations
- Johns Hopkins University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-08-11
- Volume
- 102
- Issue
- 34
- Pages
- 12065-12070
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1189326
- OpenAlex
- W2044429312
- Cited by
- 129
- References
- 85
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 11 · 2012: 6
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ente Cassa di Risparmio di Firenze
- Università degli Studi di Firenze
- Università degli Studi di Pavia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mRNA stability, protein kinase C alpha, post-transcriptional regulation, threonine phosphorylation, cytoskeleton, neuroblastoma cells, hippocampus, bryostatin 1, phorbol ester
- MeSH terms
- Animals, Cytoskeleton, Gene Expression Regulation, Hippocampus, Humans, Immunohistochemistry, Neurons, Phorbol Esters, RNA, Messenger, Blotting, Western, Signal Transduction, DNA Primers, Macrolides, GAP-43 Protein, Reverse Transcriptase Polymerase Chain Reaction, 3' Untranslated Regions, Amino Acid Motifs, RNA Stability, Cell Line, Tumor, Immunoprecipitation, Rats, Protein Kinase C-alpha, ELAV Proteins, Bryostatins
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