Abstract

Abstract Interleukin 1β‐converting enzyme (ICE)‐like proteases (caspases) play an important role in programmed cell death (apoptosis), and elucidating the consequences of their proteolytic activity is central to our understanding of the molecular mechanisms of cell death. Diverse structural and regulatory proteins and enzymes, including protein kinase Cδ, the retinoblastoma protein (a protein involved in cell survival), the DNA repair enzyme DNA‐dependent protein kinase and the nuclear lamins, undergo specific and limited endoproteolytic cleavage by various caspases during apoptosis. Since individual caspases can cleave multiple substrates, the consequences of cleavage of only a single substrate are still poorly understood. Nevertheless, proteolytic activation of protein kinase Cδ may be an important early step in the cell death pathway, and cleavage of the retinoblastoma protein could suppress its cell survival function, whereas proteolytic inactivation of DNA repair enzymes might compromise the ability of the cell to reverse DNA fragmentation. On the other hand, cleavages of nuclear and cytoplasmic structural proteins (e.g. the lamins and Gas2) appear to be required for or contribute to the dramatic rearrangements in cellular architecture that are necessary for the completion of the cell death process. An emerging theme is that parallel and sequential proteolytic activation and inactivation of key protein substrates occurs during the multiple steps of apoptosis.

Keywords

BiologyEvolutionary biologyPhilosophy

MeSH Terms

AnimalsApoptosisCysteine EndopeptidasesHumansSignal TransductionSubstrate Specificity

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Publication Info

Year
1997
Type
review
Volume
19
Issue
6
Pages
501-507
Citations
167
Access
Closed

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Cite This

Alan G. Porter, Patrick Ng, Reiner U. Jänicke (1997). Death substrates come alive. BioEssays , 19 (6) , 501-507. https://doi.org/10.1002/bies.950190609

Identifiers

DOI
10.1002/bies.950190609
PMID
9204767

Data Quality

Data completeness: 86%