https://www.cell.com/cell/pdf/S0092-8674(00)80434-1.pdf

Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade

Apoptosis, an evolutionarily conserved form of cell suicide, requires specialized machinery. The central component of this machinery is a proteolytic system involving a family of proteases called caspases. These enzymes participate in a cascade that is triggered in response to proapoptotic signals and culminates in cleavage of a set of proteins, resulting in disassembly of the cell. Understanding caspase regulation is intimately linked to the ability to rationally manipulate apoptosis for therapeutic gain.

https://science.sciencemag.org/content/sci/281/5381/1312.full.pdf

Caspases: Enemies Within

In multicellular organisms, homeostasis is maintained through a balance between cell proliferation and cell death. Although much is known about the control of cell proliferation, less is known about the control of cell death. Physiologic cell death occurs primarily through an evolutionarily conserved form of cell suicide termed apoptosis. The decision of a cell to undergo apoptosis can be influenced by a wide variety of regulatory stimuli. Recent evidence suggests that alterations in cell survival contribute to the pathogenesis of a number of human diseases, including cancer, viral infections, autoimmune diseases, neurodegenerative disorders, and AIDS (acquired immunodeficiency syndrome). Treatments designed to specifically alter the apoptotic threshold may have the potential to change the natural progression of some of these diseases.

https://science.sciencemag.org/content/sci/267/5203/1456.full.pdf

Apoptosis in the pathogenesis and treatment of disease

Induction of apoptotic program in cell-free extracts : requirement for datp and cytochrome c

Apoptosis by death factor.

The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme

An Alternatively Spliced C. elegans ced-4 RNA Encodes a Novel Cell Death Inhibitor

Described herein is the discovery that human interleukin-1β convertase (ICE) is structurally similar to the protein encoded by the C. elegans cell death gene, ced-3. Comparative and mutational analyses of the two proteins, together with previous observations, suggest that the Ced-3 protein may be a cysteine protease like ICE and that ICE may be a human equivalent of the nematode cell death gene. Another mammalian protein, the murine NEDD-2 protein, was also found to be similar to Ced-3. The NEDD-2 gene is implicated in the development of the murine central nervous system. On the basis of these findings, novel drugs for enhancing or inhibiting the activity of ICE, ced-3, or related genes are provided. Such drugs may be useful for treating inflammatory diseases and/or diseases characterized by cell deaths, as well as cancers, autoimmune disorders, infections, and hair growth and hair loss. Furthermore, such drugs may be useful for controlling pests, parasites and genetically engineered organisms. Furthermore, novel inhibitors of the activity of ced-3, ICE and related genes are described which comprise portions of the genes or their encoded products.

Relatedness of human interleukin-1β convertase gene to a C. elegans cell death gene, inhibitory portions of these genes and uses therefor

Described herein are genes shown to be essential for programmed cell death in C. elegans, their encoded products (RNA and polypeptides), antibodies directed against the encoded polypeptides; probes for identifying structurally related genes and bioassays for identifying functionally related cell death genes from various organisms; methods and agents for altering (increasing or decreasing) the activity of the cell death genes and, thus, of altering cell death; and uses therefor. Specifically, two genes shown to be essential for almost all of the cell deaths which occur in the development of C. elegans, referred to as ced-3 and ced-4, have been cloned, sequenced and characterized.

Shai Shaham

Papers

The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme

An Alternatively Spliced C. elegans ced-4 RNA Encodes a Novel Cell Death Inhibitor

Relatedness of human interleukin-1β convertase gene to a C. elegans cell death gene, inhibitory portions of these genes and uses therefor

Cloning and characterization of the cell death genes ced-3 and ced-4

Inhibitors of ced-3 and related proteins