Caspases are intracellular
proteases that are best known for their function in apoptosis signaling. It has become evident that many
caspases also function in other signaling pathways that propagate cell proliferation and
inflammation, but studies on the inflammatory function of
caspases have mainly been limited to caspase-1-mediated
cytokine processing. Emerging evidence, however, indicates an important contribution of
caspases as mediators or regulators of nuclear factor-κB (NF-κB) signaling, which plays a key role in
inflammation and immunity. Much still needs to be learned about the mechanisms that govern the activation and regulation of NF-κB by
caspases, and this review provides an update of this area. Whereas apoptosis signaling is dependent on the catalytic activity of
caspases, they mainly act as scaffolding platforms for other signaling
proteins in the case of NF-κB signaling.
Caspase proteolytic activity, however, counteracts the pro-survival function of NF-κB by cleaving specific signaling molecules. A striking exception is the
paracaspase mucosa-associated lymphoid tissue 1 (MALT1), whose adaptor and proteolytic activity are both needed to initiate a full blown NF-κB response in
antigen-stimulated lymphocytes. Understanding the role of
caspases and MALT1 in the regulation of NF-κB signaling is of high interest for therapeutic
immunomodulation.