The tumor suppressor Sef is a scaffold for the classical NF-κB/RELA:P50 signaling module.

The classical NF-κB transcription factor (RelA:p50) and the tumor suppressor Sef axis constitute a negative regulatory loop in which Sef, a target of NF-κB/RelA:p50, fine-tunes NF-κB/RelA:p50 transcriptional-activation in response to inflammatory stimuli trough binding to p50. Similar to the inhibitor IκBα, Sef sequesters NF-κB/RelA:p50 in the cytoplasm of unstimulated cells. Despite its key roles in regulating multiple cellular processes and its potential role as mediator between inflammation and cancer, Sef structural domains required to fulfill its tasks are poorly characterized, and how Sef specificity towards RelA:p50 is achieved is unknown.