Question

Because one of the targets of NF-κB activation is the gene for I-κBα, the cytoplasmic inhibitor of NF-κB, a negative feedback loop is established that limits the NF-κB response to a short duration when exposed to a sustained stimulation by tumor necrosis factor α (TNFα), which activates NF-κB. True or False?

1) True
2) False

Answer 1

The statement is true; NF-κB activation by TNFα triggers a negative feedback loop via the gene for I-κBα, limiting the response. Phosphorylation by PKC inactivates I-κB, allowing NF-κB to initiate transcription, including that of I-κBα itself, which inhibits over-reactivity.

Step-by-step explanation:

The statement that the activation of NF-κB by tumor necrosis factor α (TNFα) establishes a negative feedback loop through the gene for I-κBα, limiting the NF-κB response to a short duration, is true. The negative feedback loop operates because NF-κB, once activated, enters the nucleus and stimulates the production of I-κBα. The newly synthesized I-κBα then binds to NF-κB, preventing it from activating additional target genes, thus restraining the signal and preventing over-reactivity.

Phosphorylation and NF-κB Activation

In the context of gene regulation, phosphorylation can greatly influence the activity of proteins. Protein kinase C (PKC) can phosphorylate I-κB, the inhibitor of NF-κB, causing I-κB to release NF-κB. This allows NF-κB to translocate to the nucleus and commence transcription of genes, including those involved in cellular metabolism and apoptosis under certain conditions such as cell infection or damage. This process exemplifies the regulation of transcription factors in cell signaling pathways, which has significant implications for disease treatment, including cancer.