Role for IKK2 in muscle: waste not, want not.
Activation of transcription factor NF-kappaB, the major regulator of the inflammatory response, depends on the inhibitor of NF-kappaB kinase (IKK) complex, which is composed of 2 catalytic subunits, IKK1 and IKK2 (also known as IKKalpha and IKKbeta), and a regulatory subunit, IKKgamma (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-kappaB 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.
Karin
Michael
M
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California 92093, USA. karinoffice@ucsd.edu
D000818:Animals; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D053580:Muscle Strength; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D009136:Muscular Dystrophies / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy
D051550:I-kappa B Kinase