摘要
Caspase regulation and activation have been extensively studied since the discovery of this class of proteases almost two decades ago, yet surprisingly few tools are available that can be used to monitor individual caspase activities [ 1 ]. The most commonly used tools include caspase-specific anti-sera as well as fluorogenic substrates and inhibitors. Unfortunately, antibody reagents often do not provide an accurate measure of caspase activity since several caspase family members (caspases 8/10 and 9) do not require proteolytic processing for activation [2, 3]. Furthermore, recent evidence suggests that caspase-7 (an executioner caspase) activation occurs via a catalytically active full-length intermediate that cannot be differentiated from the non-cleaved inactive zymogen using antibodies [4, 5].
Dear Editor:Caspase regulation and activation have been extensivelystudied since the discovery of this class of proteases almosttwo decades ago, yet surprisingly few tools are availablethat can be used to monitor individual caspase activities[1]. The most commonly used tools include caspase-specificanti-sera as well as fluorogenic substrates and inhibitors.Unfortunately, antibody reagents often do not provide anaccurate measure of caspase activity since several caspasefamily members (caspases 8/10 and 9) do not require pro-teolytic processing for activation [2,3].Furthermore,recentevidence suggests that caspase-7(an executioner caspase)activation occurs via a catalytically active full-length inter-mediate that cannot be differentiated from the non-cleavedinactive zymogen using antibodies[4,5].As an alternative to antibody-based reagents,smallmolecule substrates and inhibitors can be used to directlymonitor caspase activity and a relatively large number ofcaspase substrates,inhibitors,and activity-based probes arenow commercially available.These reagents have begunto find widespread use in cell biological and biochemicalstudies of caspase function.In most cases,these tools areused as selective reagents to assess the contribution ofspecific caspases to a given apoptotic pathway.