Goldilocks and the E3 ligase

Our innate immune system provides the first line of defense against invading pathogens. However, hyperactivation of these defenses can lead to inflammatory syndromes such as arthritis. Controlling the transcriptional programs that drive the innate immune response is therefore critical. In work recently published in eLife, the Versteeg lab has identified a factor essential for the degradation of the transcription factor IRF1, a key driver of the innate immune response. The work establishes a cellular mechanism by which cells maintain IRF1 levels in a so-called ‘Goldilocks zone’, thereby guarding against IRF1-driven inflammation.