The zinc finger domain of IKKγ (NEMO) protein in health and disease

Research output: Contribution to journalArticle

Abstract

Inhibitor of κB kinase (IKK) gamma (IKKγ), also known as nuclear factor κB (NF-κB) essential modulator (NEMO), is a component of the IKK complex that is essential for the activation of the NF-κB pathway. The NF-κB pathway plays a major role in the regulation of the expression of genes that are involved in immune response, inflammation, cell adhesion, cell survival and development. As part of the IKK complex, IKKγ plays a regulatory role by linking the complex to upstream signalling molecules. IKKγ contains two coiled-coil regions, a leucine zipper domain and a highly conserved zinc finger domain. Mutations affecting IKKγ have been associated with X-linked hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID), with the majority of these mutations affecting the C-terminal region of the protein where the zinc finger is located. The zinc finger of IKKγ is needed for NF-κB activation in a cell- and stimulus-specific manner. The major mechanism by which the zinc finger plays this role appears to be the recognition of polyubiquitinated upstream signalling intermediates. This assertion reinforces the current notion that ubiquitination plays a major role in mediating protein-protein interactions in the NF-κB signalling pathway. Because the zinc finger domain of IKKγ is very likely involved in mediating interactions with ubiquitinated proteins, investigations that look for upstream activators or inhibitors of the IKK complex that bind to and interact with the zinc finger of IKKγ are required to gain a better insight into the exact roles of this domain and into the pathogenesis of HED-ID.

Original languageEnglish (US)
Pages (from-to)2404-2414
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Zinc Fingers
Health
Proteins
I-kappa B Kinase
Ubiquitinated Proteins
Leucine Zippers
Mutation
Ubiquitination
Gene Expression Regulation
Cell Adhesion
Cell Survival
Phosphotransferases
Inflammation

Keywords

  • Ectodermal dysplasia
  • Hyper IgM syndrome
  • IKKgamma
  • Immune deficiency
  • NEMO
  • Ubiquitination
  • Zinc finger

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

The zinc finger domain of IKKγ (NEMO) protein in health and disease. / Shifera, Amde Selassie.

In: Journal of Cellular and Molecular Medicine, Vol. 14, No. 10, 10.2010, p. 2404-2414.

Research output: Contribution to journalArticle

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