NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100

Mol Cell. 2001 Feb;7(2):401-9. doi: 10.1016/s1097-2765(01)00187-3.

Abstract

Processing of the nf(kappa)b2 gene product p100 to generate p52 is an important step in NF-kappaB regulation. We show that this step is negatively regulated by a processing-inhibitory domain (PID) within p100 and positively regulated by the NF-kappaB-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 nf(kappa)b2 knockout mice exhibit similar immune deficiencies.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Genotype
  • Humans
  • Immunoblotting
  • Mice
  • Mice, Mutant Strains
  • Molecular Weight
  • Mutation
  • NF-kappa B / chemistry*
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Substrate Specificity
  • Transfection
  • Ubiquitins / metabolism

Substances

  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Ubiquitins
  • Phosphoserine
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase