查看文章

Transcriptional control of the vast majority of genes involved in the inflammatory response requires the nuclear factor κB (NF-κB) family of transcription factors. Stimulation and termination of NF-κB activity are subject to stringent spatiotemporal control. According to the classical model of NF-κB regulation, both activation and termination mechanisms are centered on inhibitor of NF-κB (IκB) proteins. Whereas activation of NF-κB requires degradation of the IκBs, the main mechanism responsible for termination of NF-κB activity is the resynthesis of a specific IκB, IκBα, which sequesters NF-κB dimers in the nucleus and translocates them to the cytoplasm in an inactive form. Studies now show that an additional mechanism that is required to prevent the uncontrolled activity of NF-κB proteins is their nuclear degradation. At least two E3 ubiquitin ligases, one of which seems to be essential for control of nuclear NF-κB p65 …