ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Threonine 149 phosphorylation enhances ΔFosB transcriptional activity to control psychomotor responses to cocaine.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Voluntary Physical Activity Modulates Brain ΔFOSB and Alters Coactivation Networks in Male and Female Mice.eNeuro · 2026Article
- Brain-wide induction of ΔFOSB and altered co-activation networks in a rat model for exercise training.Translational psychiatry · 2026Article
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- The Role of ΔFosB in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies.Molecular neurobiology · 2025Review
- Voluntary Running and Estrous Cycle Modulate ΔFOSB in the Suprachiasmatic Nucleus of the Wistar Rat.Journal of circadian rhythms · 2025Article
- Amelioration of Nicotine-Induced Conditioned Place Preference Behaviors in Mice by an FABP3 Inhibitor.International journal of molecular sciences · 2023Article
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- ΔFOSB: A Potentially Druggable Master Orchestrator of Activity-Dependent Gene Expression.ACS chemical neuroscience · 2022Article
- The Role of CaMKII and ERK Signaling in Addiction.International journal of molecular sciences · 2021Review
- Self-assembly of the bZIP transcription factor ΔFosB.Current research in structural biology · 2020Article
- Epigenetic Regulation of HippocampalThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- A novel role for E2F3b in regulating cocaine action in the prefrontal cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain's Reward Circuitry.Biological psychiatry · 2018Article
- Emerging role of viral vectors for circuit-specific gene interrogation and manipulation in rodent brain.Pharmacology, biochemistry, and behavior · 2018Review
- GIRK currents in VTA dopamine neurons control the sensitivity of mice to cocaine-induced locomotor sensitization.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Transcription Factor E2F3a in Nucleus Accumbens Affects Cocaine Action via Transcription and Alternative Splicing.Biological psychiatry · 2018Article
- Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Antidyskinetic Effects of MEK Inhibitor Are Associated with Multiple Neurochemical Alterations in the Striatum of Hemiparkinsonian Rats.Frontiers in neuroscience · 2017Article
- Alterations of the Host Microbiome Affect Behavioral Responses to Cocaine.Scientific reports · 2016Article
- ∆FosB: a transcriptional regulator of stress and antidepressant responses.European journal of pharmacology · 2015Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Stable changes in neuronal gene expression have been studied as mediators of addicted states. Of particular interest is the transcription factor ΔFosB, a truncated and stable FosB gene product whose expression in nucleus accumbens (NAc), a key reward region, is induced by chronic exposure to virtually all drugs of abuse and regulates their psychomotor and rewarding effects. Phosphorylation at Ser(27) contributes to ΔFosB's stability and accumulation following repeated exposure to drugs, and our recent work demonstrates that the protein kinase CaMKIIα phosphorylates ΔFosB at Ser(27) and regulates its stability in vivo. Here, we identify two additional sites on ΔFosB that are phosphorylated in vitro by CaMKIIα, Thr(149) and Thr(180), and demonstrate their regulation in vivo by chronic cocaine. We show that phosphomimetic mutation of Thr(149) (T149D) dramatically increases AP-1 transcriptional activity while alanine mutation does not affect transcriptional activity when compared with wild-type (WT) ΔFosB. Using in vivo viral-mediated gene transfer of ΔFosB-T149D or ΔFosB-T149A in mouse NAc, we determined that overexpression of ΔFosB-T149D in NAc leads to greater locomotor activity in response to an initial low dose of cocaine than does WT ΔFosB, while overexpression of ΔFosB-T149A does not produce the psychomotor sensitization to chronic low-dose cocaine seen after overexpression of WT ΔFosB and abrogates the sensitization seen in control animals at higher cocaine doses. We further demonstrate that mutation of Thr(149) does not affect the stability of ΔFosB overexpressed in mouse NAc, suggesting that the behavioral effects of these mutations are driven by their altered transcriptional properties.
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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.