Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/24122
Full metadata record
DC FieldValueLanguage
dc.contributor.authorMacFarlane, Marion-
dc.contributor.authorCain, Kelvin-
dc.contributor.authorSun, Xiao-Ming-
dc.contributor.authorAlnemri, E. S.-
dc.contributor.authorCohen, Gerald M.-
dc.date.accessioned2012-10-24T09:14:17Z-
dc.date.available2012-10-24T09:14:17Z-
dc.date.issued1997-4-21-
dc.identifier.citationJournal of Cell Biology, 1997, 137 (2), pp. 469-479-
dc.identifier.issn0021-9525-
dc.identifier.urihttp://hdl.handle.net/2381/24122-
dc.identifier.urihttp://jcb.rupress.org/content/137/2/469-
dc.description.abstractIdentification of the processing/activation of multiple interleukin-1β converting enzyme (ICE)–like proteases and their target substrates in the intact cell is critical to our understanding of the apoptotic process. In this study we demonstrate processing/activation of at least four ICE-like proteases during the execution phase of apoptosis in human monocytic tumor THP.1 cells. Apoptosis was accompanied by processing of Ich-1, CPP32, and Mch3α to their catalytically active subunits, and lysates from these cells displayed a proteolytic activity with kinetics, characteristic of CPP32/Mch3α but not of ICE. Fluorescence-activated cell sorting was used to obtain pure populations of normal and apoptotic cells. In apoptotic cells, extensive cleavage of Ich-1, CPP32, and Mch3α was observed together with proteolysis of the ICE-like protease substrates, poly (ADP-ribose) polymerase (PARP), the 70-kD protein component of U1 small nuclear ribonucleoprotein (U170K), and lamins A/B. In contrast, no cleavage of CPP32, Mch3α or the substrates was observed in normal cells. In cells exposed to an apoptotic stimulus, some processing of Ich-1 was detected in morphologically normal cells, suggesting that cleavage of Ich-1 may occur early in the apoptotic process. The ICE-like protease inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD.FMK), inhibited apoptosis and cleavage of Ich-1, CPP32, Mch3α, Mch2α, PARP, U1-70K, and lamins. These results suggest that Z-VAD.FMK inhibits apoptosis by inhibiting a key effector protease upstream of Ich-1, CPP32, Mch3α, and Mch2α. Together these observations demonstrate that processing/activation of Ich-1, CPP32, Mch3α, and Mch2α accompanies the execution phase of apoptosis in THP.1 cells. This is the first demonstration of the activation of at least four ICE-like proteases in apoptotic cells, providing further evidence for a requirement for the activation of multiple ICE-like proteases during apoptosis.-
dc.publisherRockefeller University Press-
dc.rights© 1997 Rockefeller University Press CC BY-NC-SA-
dc.sourceScopus-
dc.source.urihttp://www.scopus.com/home.url-
dc.titleProcessing/activation of at least four interleukin-1β converting enzyme-like proteases occurs during the execution phase of apoptosis in human monocytic tumor cells-
dc.typeJournal Article-
dc.identifier.doi10.1083/jcb.137.2.469-
dc.description.irispid77187-
Appears in Collections:Published Articles, Dept. of Biochemistry



Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.