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Commonly used caspase inhibitors designed based on substrate specificity profiles lack selectivity 被引量:1

Commonly used caspase inhibitors designed based on substrate specificity profiles lack selectivity
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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.
出处 《Cell Research》 SCIE CAS CSCD 2006年第12期961-963,共3页 细胞研究(英文版)
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  • 1Janicke RU, Sohn D, Totzke G, Schulze-OsthoffK. Caspase-10 in mouse or not? Science 2006; 312:1874.
  • 2Boatright KM, Renatus M, Scott FL, et al. A unified model for apical caspase activation. Mol Cell 2003; 11:529-541.
  • 3Pop C, Timmer J, Sperandio S, Salvesen GS. The apoptosome activates caspase-9 by dimerization. Mol Cell 2006; 22:269-275.
  • 4Denault JB, Bekes M, Scott FL, Sexton KM, Bogyo M, Salvesen GS. Engineered hybrid dimers: tracking the activation pathway of caspase-7. Mol Cell 2006; 23:523-533.
  • 5Berger AB, Witte MD, Denault JB, et al. Identification of early intermediates ofcaspase activation using selective inhibitors and activity-based probes. Mol Cell 2006; 23:509-521.
  • 6Thomberry NA, Rano TA, Peterson EP, et al. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 1997; 272:17907-17911.
  • 7Thomberry NA, Peterson EP, Zhao J J, Howard AD, Griffin PR,Chapman KT. Inactivation of interleukin-1 beta converting enzyme by peptide (acyloxy)methyl ketones. Biochemistry 1994;33:3934-3940.
  • 8Kato D, Boatright KM, Berger AB, et al. Activity-based probes that target diverse cysteine protease families. Nat Chem Biol 2005; 1:33-38.
  • 9Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996; 86:147-157.

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