The zinc finger of NEMO is a functional ubiquitin-binding domain

J Biol Chem. 2009 Jan 30;284(5):2902-2907. doi: 10.1074/jbc.M806655200. Epub 2008 Nov 25.

Abstract

NEMO (NF-kappaB essential modulator) is a regulatory protein essential to the canonical NF-kappaB signaling pathway, notably involved in immune and inflammatory responses, apoptosis, and oncogenesis. Here, we report that the zinc finger (ZF) motif, located in the regulatory C-terminal half of NEMO, forms a specific complex with ubiquitin. We have investigated the NEMO ZF-ubiquitin interaction and proposed a structural model of the complex based on NMR, fluorescence, and mutagenesis data and on the sequence homology with the polymerase eta ubiquitin-binding zinc finger involved in DNA repair. Functional complementation assays and in vivo pull-down experiments further show that ZF residues involved in ubiquitin binding are functionally important and required for NF-kappaB signaling in response to tumor necrosis factor-alpha. Thus, our findings indicate that NEMOZFisa bona fide ubiquitin-binding domain of the ubiquitin-binding zinc finger type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Blotting, Western
  • Cell Line
  • Genetic Complementation Test
  • Humans
  • Immunoprecipitation
  • Jurkat Cells
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Sequence Homology, Amino Acid
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*
  • Zinc Fingers*

Substances

  • Ubiquitin