from Part I - General Principles of Cell Death
Published online by Cambridge University Press: 07 September 2011
Protease Signaling in Apoptosis and Inflammation
In 1992 two groups independently reported the identity of a human protease responsible for activating the precursor of interleukin-1β, naming it interleukin-1β converting enzyme (ICE). Several months later, one of the key genes governing the commitment to apoptosis in Caenorhabditis elegans – CED3 – was demonstrated to show homology with ICE. These publications initiated a successful search by many groups over the ensuing years for mammalian ICE homologs that should govern cell death. Today these proteases are known as caspases. Of the 11 caspases in humans, 7 are considered to be involved primarily in apoptosis, three are considered to be involved primarily in proinflammatory cytokine activation, and one is involved in keratinocyte differentiation (Figure 1-1). How cells learned to employ closely related proteases to execute two opposing phenotypes – apoptosis and inflammation – is strongly debated, and this chapter incorporates some discussion on this tricky issue.
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