cytoplasmic sequestering of NF-kappaB

Definition

Target type: biologicalprocess

The selective interaction of the transcription factor NF-kappaB with specific molecules in the cytoplasm, thereby inhibiting its translocation into the nucleus. [GOC:jl]

NF-κB, a ubiquitous transcription factor, plays a pivotal role in regulating gene expression in response to a myriad of stimuli, including inflammation, stress, and infection. Under basal conditions, NF-κB is sequestered in the cytoplasm, bound to an inhibitory protein called IκBα. This interaction masks the nuclear localization signal of NF-κB, preventing its translocation to the nucleus and activation of target genes.

Upon cellular activation, a signaling cascade is initiated, typically through the engagement of cell surface receptors. This triggers the activation of specific kinases, such as the IκB kinase (IKK) complex, which phosphorylates IκBα at specific serine residues. Phosphorylation of IκBα marks it for ubiquitination by a multi-protein complex known as the SCF complex. Ubiquitination is a post-translational modification involving the attachment of a polyubiquitin chain to a target protein. In the case of IκBα, ubiquitination serves as a signal for its proteasomal degradation.

The proteasome, a multi-protein complex responsible for the degradation of misfolded or damaged proteins, recognizes and degrades polyubiquitinated IκBα. The degradation of IκBα releases NF-κB, allowing it to translocate to the nucleus. Once in the nucleus, NF-κB binds to specific DNA sequences in the promoters of target genes, inducing their transcription.

The cytoplasmic sequestration of NF-κB is essential for maintaining cellular homeostasis. It prevents inappropriate activation of pro-inflammatory and pro-survival genes, which could lead to dysregulated immune responses and uncontrolled cell growth. When NF-κB is released from its cytoplasmic anchor, it can rapidly translocate to the nucleus and induce the expression of genes involved in inflammation, immunity, cell survival, and proliferation. This tight regulation of NF-κB activity is crucial for maintaining a delicate balance between immune activation and suppression, ensuring that cells respond appropriately to stimuli while preventing uncontrolled inflammation and disease.'
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Proteins (2)

Compounds (7)