Role for IKK2 in muscle: Waste not, want not

Abstract

Activation of transcription factor NF-κB, the major regulator of the inflammatory response, depends on the inhibitor of NF-κB kinase (IKK) complex, which is composed of 2 catalytic subunits, IKK1 and IKK2 (also known as IKKα and IKKβ), and a regulatory subunit, IKKγ (also known as NEMO). In this issue of the JCI, Mourkioti et al. show that muscle-specific disruption in mice of the gene encoding IKK2 prevents NF-κB activation in response to denervation or toxin-induced injury (see the related article beginning on page 2945). Importantly, this genetic manipulation prevents muscle wasting, thereby providing strong evidence in support of a major pathogenic role for inflammation in a variety of muscular dystrophies characterized by progressive muscle fiber degeneration.