Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.
Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity
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Jeremy Saklatvala, Hideaki Nagase, Guy Salvesen, Roy A. Black, John R. Doedens, Rajeev Mahimkar, Richard Johnson, Lin Guo, Alison Wallace, Duke Virca, June Eisenman, Jennifer Slack, Beverly Castner, Susan W. Sunnarborg, David C. Lee, Rebecca Cowling, Guixian Jin, Keith Charrier, Jacques J. Peschon, Ray Paxton; Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity. Biochem Soc Symp 1 September 2003; 70 39–52. doi: https://doi.org/10.1042/bss0700039
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