NF-κB-inducing kinase regulates the processing of NF-κB2 p100

Gutian Xiao, Edward W. Harhaj, Shao Cong Sun

Research output: Contribution to journalArticle

593 Scopus citations

Abstract

Processing of the nfκb2 gene product p100 to generate p52 is an important step in NF-κB regulation. We show that this step is negatively regulated by a processing-inhibitory domain (PID) within p100 and positively regulated by the NF-κB-inducing kinase (NIK). While the PID suppresses the constitutive processing of p100, NIK induces p100 processing by stimulating site-specific phosphorylation and ubiquitination of this precursor protein. Further, a natural mutation of the gene encoding NIK in alymphoplasia (aly) mice cripples the function of NIK in p100 processing, causing a severe defect in p52 production. These data suggest that NIK is a specific kinase regulating p100 processing and explain why the aly and nfκb2 knockout mice exhibit similar immune deficiencies.

Original languageEnglish (US)
Pages (from-to)401-409
Number of pages9
JournalMolecular cell
Volume7
Issue number2
DOIs
StatePublished - Jan 1 2001

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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