title: Death substrates come alive.
abstract: Interleukin 1 beta-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 C delta, 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 C delta 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.
authors.affiliation: Institute of Molecular and Cell Biology, National University of Singapore, Republic of Singapore. mcbagp@leonis.nus.sg
authors.forename: A G
authors.initials: AG
authors.lastname: Porter
authors.forename: P
authors.initials: P
authors.lastname: Ng
authors.forename: R U
authors.initials: RU
authors.lastname: Jänicke
mesh_terms: D000818:Animals; D017209:Apoptosis; D003546:Cysteine Endopeptidases; D006801:Humans; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D003546:Cysteine Endopeptidases