Lazebnik, Y. A., Takahashi, A., Moir, R. D., Goldman, R. D., Poirier, G. G., Kaufmann, S. H., Earnshaw, W. C. (1995) Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. Proc Natl Acad Sci U S A, 92 (20). pp. 9042-9046. ISSN 0027-8424
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Abstract
Although specific proteinases play a critical role in the active phase of apoptosis, their substrates are largely unknown. We previously identified poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have used a cell-free system to characterize proteinase(s) that cleave the nuclear lamins during apoptosis. Lamin cleavage during apoptosis requires the action of a second ICE-like enyzme, which exhibits kinetics of cleavage and a profile of sensitivity to specific inhibitors that is distinct from the PARP proteinase. Thus, multiple ICE-like enzymes are required for apoptotic events in these cell-free extracts. Inhibition of the lamin proteinase with tosyllysine "chloromethyl ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin into apoptotic bodies. Under these conditions, the nuclear DNA is fully cleaved to a nucleosomal ladder. Our studies reveal that the lamin proteinase and the fragmentation nuclease function in independent parallel pathways during the final stages of apoptotic execution. Neither pathway alone is sufficient for completion of nuclear apoptosis. Instead, the various activities cooperate to drive the disassembly of the nucleus.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Amino Acid Sequence Apoptosis Cell Line Cell Nucleus Cell-Free System Endopeptidases HeLa Cells Humans Kinetics Lamins Lung Neoplasms Molecular Sequence Data Nuclear Proteins Poly(ADP-ribose) Polymerases Protease Inhibitors Recombinant Proteins Structure-Activity Relationship Substrate Specificity Tumor Cells, Cultured |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions |
| CSHL Authors: | |
| Communities: | CSHL labs > Labeznik lab |
| Depositing User: | Matt Covey |
| Date: | 1995 |
| Date Deposited: | 12 Dec 2012 17:32 |
| Last Modified: | 09 Nov 2017 19:34 |
| PMCID: | PMC40920 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/26403 |
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