http://www.proteolysis.org Caspase-7 is a member of the caspase (cysteine aspartate protase) family of proteins, and has been shown to be an executioner protein of apoptosis. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing by upstream caspases (caspase-8, -9)at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme in the form of a heterotetramer. The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and induces apoptosis. Alternative splicing results in four transcript variants, encoding three distinct isoforms. Design & production: Kosi Gramatikoff, PhD; client: Guy S. Salvesen, PhD

http://www.proteolysis.org Caspase 3 is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6, 7, and 9; and the protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein. http://www.proteolysis.org/proteases/m_summarypg/pmap.22035

http://www.proteolysis.org Caspase 8 is member of the cysteine-aspartic acid protease (caspase) family. The NH2-terminal region of caspase-8 contains two death effector domains (DEDs), through which it binds the DED of Fas-associated death domain (FADD). The COOH-terminal region of caspase-8 is related to the interleukin-1beta converting enzyme (ICE) family of proteases. FADD mediates the recruitment of caspase-8 to tumor necrosis factor receptor 1 (TNF-R1), where caspase-8 becomes activated, presumably by self-cleavage, and in turn initiates a proteolytic cascade that ultimately leads to apoptosis. Two important examples of the direct initiation of apoptotic mechanisms in mammals include the TNF-induced (tumour necrosis factor) model and the Fas-Fas ligand-mediated model, both involving receptors of the TNF receptor (TNFR) family coupled to extrinsic signals. TNF is a cytokine produced mainly by activated macrophages, and is the major extrinsic mediator of apoptosis. Most cells in the human body have two receptors for TNF: TNF-R1 and TNF-R2. The binding of TNF to TNF-R1 has been shown to initiate the pathway that leads to caspase activation via the intermediate membrane proteins TNF receptor-associated death domain (TRADD) and Fas-associated death domain protein (FADD). Design & production: Kosi Gramatikoff, PhD; client: John C. Reed, Md PhD

http://www.proteolysis.org Caspase-7 is a member of the caspase (cysteine aspartate protase) family of proteins, and has been shown to be an executioner protein of apoptosis. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing by upstream caspases (caspase-8, -9)at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme in the form of a heterotetramer. The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and induces apoptosis. Alternative splicing results in four transcript variants, encoding three distinct isoforms. Design & production: Kosi Gramatikoff, PhD; client: Guy S. Salvesen, PhD

http://www.proteolysis.org/proteases/m_summarypg/pmap.22035 Caspase-3 is a death protease, catalyzing the specific cleavage of many key cellular proteins. Pathways to caspase-3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c release and caspase-9 function. Caspase-3 is essential for normal brain development and is important or essential in other apoptotic scenarios in a remarkable tissue-, cell type- or death stimulus-specific manner. Caspase-3 is also required for some typical hallmarks of apoptosis, and is indispensable for apoptotic chromatin condensation and DNA fragmentation in all cell types examined. Apoptotic proteins that target mitochondria affect them in different ways; they may cause mitochondrial swelling through the formation of membrane pores, or they may increase the permeability of the mitochondrial membrane and cause apoptotic effectors to leak out. Cytochrome c is also released from mitochondria due to formation of a channel, MAC, in the outer mitochondrial membrane, and serves a regulatory function as it precedes morphological change associated with apoptosis. Once cytochrome c is released it binds with Apaf-1 and ATP, which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn activates the effector caspase-3. Design & production: Kosi Gramatikoff, PhD; client: John C. Reed, MD PhD

aka Cell Death. Apoptosis is a process where a cell is degraded in order for it to be ultimately engulfed and recycled. Apoptosis can occur when a cell has become mutated and is on the verge of becoming a cancer. Apoptosis is also the reason why we don't have webbed hands and feet. What basically happens is that the killer t cell communicates with the diseased cell by adhering to it by binding its death ligand to the death receptor on the diseased cell. This causes adapter proteins to attach to the cytosolic side of the receptor. This leads to a signal cascade which involves the recruitment of various other proteins and ultimately results in the death of the cell.

Apoptosis Detection Methods

Interaction between neurons and glia in aging and disease