Duration of Nuclear NF-κB Action Regulated by Reversible Acetylation
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Implication
Experimental study demonstrates that HDAC3 deacetylation of RelA terminates nuclear NF-κB activity in mammalian cells, indicating an essential molecular switch for inflammatory timing.
Key Points
- To identify the molecular mechanisms that regulate the termination and duration of nuclear NF-κB transcriptional activity.
- Analyzed the post-translational acetylation state of the NF-κB RelA subunit.
- Characterized binding interactions between acetylated and deacetylated RelA, the IκBα inhibitor, and histone deacetylase 3 (HDAC3).
- Assessed nuclear export pathways mediating the return of latent NF-κB complexes to the cytoplasm.
- Inducible acetylation of the RelA subunit significantly impaired its binding affinity for the inhibitory protein IκBα.
- Histone deacetylase 3 deacetylated RelA, restoring strong complex formation with IκBα and triggering nuclear export through a CRM-1-dependent pathway.
- HDAC3-directed deacetylation functioned as an intranuclear molecular switch that regulated the lifespan of the transcriptional response and replenished cytoplasmic NF-κB stores.
Cite This Study
Chen et al. (2001) studied this question.