The nuclear signaling of NF-κB: Current knowledge, new insights, and future perspectives

Fengyi Wan, Michael J. Lenardo

Research output: Contribution to journalReview articlepeer-review

260 Scopus citations


The nuclear factor-kappa B (NF-κB) transcription factor plays a critical role in diverse cellular processes associated with proliferation, cell death, development, as well as innate and adaptive immune responses. NF-κB is normally sequestered in the cytoplasm by a family of inhibitory proteins known as inhibitors of NF-κB (IκBs). The signal pathways leading to the liberation and nuclear accumulation of NF-κB, which can be activated by a wide variety of stimuli, have been extensively studied in the past two decades. After gaining access to the nucleus, NF-κB must be actively regulated to execute its fundamental function as a transcription factor. Recent studies have highlighted the importance of nuclear signaling in the regulation of NF-κB transcriptional activity. A non-Rel subunit of NF-κB, ribosomal protein S3 (RPS3), and numerous other nuclear regulators of NF-κB, including Akirin, Nurr1, SIRT6, and others, have recently been identified, unveiling novel and exciting layers of regulatory specificity for NF-κB in the nucleus. Further insights into the nuclear events that govern NF-κB function will deepen our understanding of the elegant control of its transcriptional activity and better inform the potential rational design of therapeutics for NF-κB-associated diseases.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalCell Research
Issue number1
StatePublished - Jan 2010
Externally publishedYes


  • DNA binding
  • Immunity
  • RPS3

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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