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Apoptosis is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic,single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing,cell shrinkage,nuclear fragmentation,chromatin condensation,DNA fragmentation,and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old,each day the approximate loss is 20 to 30 billion cells.
The cytochrome complex,or cyt c,is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. It transfers electrons between Complexes III and IV. Cytochrome c is highly water-soluble,unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms,but does not bind oxygen. It also plays a major role in cell apoptosis. In humans,cytochrome c is encoded by the CYCS gene.
Caspases are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity –a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009,there are 12 confirmed caspases in humans and 10 in mice,carrying out a variety of cellular functions.
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols,SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences,thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop.
The BH3 interacting-domain death agonist,or BID,gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains,and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.
The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family,a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting,unlike most other members of the Bcl-2 family. After activation,it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.
Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. It is an initiator caspase,critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist,such as Mus musculus and Pan troglodytes.
X-linked inhibitor of apoptosis protein (XIAP),also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4),is a protein that stops apoptotic cell death. In humans,this protein (XIAP) is produced by a gene named XIAP gene located on the X chromosome.
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds,lizards,lissamphibians,and teleosts.
Caspase-7,apoptosis-related cysteine peptidase,also known as CASP7,is a human protein encoded by the CASP7 gene. CASP7 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds,lizards,lissamphibians,and teleosts.
Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds,lizards,lissamphibians,and teleosts. Caspase-6 has known functions in apoptosis,early immune response and neurodegeneration in Huntington's and Alzheimer's disease.
Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the SREBF2 gene.
Caspase-10 is an enzyme that,in humans,is encoded by the CASP10 gene.
Apoptotic protease activating factor 1,also known as APAF1,is a human homolog of C. elegans CED-4 gene.
Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. It breaks up the DNA during apoptosis and promotes cell differentiation. It is usually an inactive monomer inhibited by ICAD. This is cleaved before dimerization.
Necroptosis is a programmed form of necrosis,or inflammatory cell death. Conventionally,necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens,in contrast to orderly,programmed cell death via apoptosis. The discovery of necroptosis showed that cells can execute necrosis in a programmed fashion and that apoptosis is not always the preferred form of cell death. Furthermore,the immunogenic nature of necroptosis favors its participation in certain circumstances,such as aiding in defence against pathogens by the immune system. Necroptosis is well defined as a viral defense mechanism,allowing the cell to undergo "cellular suicide" in a caspase-independent fashion in the presence of viral caspase inhibitors to restrict virus replication. In addition to being a response to disease,necroptosis has also been characterized as a component of inflammatory diseases such as Crohn's disease,pancreatitis,and myocardial infarction.
Caspase-2 is an enzyme. This enzyme catalyses the following chemical reaction
The Early 35 kDa protein,or P35 in short,is a baculoviral protein that inhibits apoptosis in the cells infected by the virus. Although baculoviruses infect only invertebrates in nature,ectopic expression of P35 in vertebrate animals and cells also results in inhibition of apoptosis,thus indicating a universal mechanism. P35 has been shown to be a caspase inhibitor with a very wide spectrum of activity both in regard to inhibited caspase types and to species in which the mechanism is conserved.
Junying Yuan is the Elizabeth D. Hay Professor of Cell Biology at Harvard Medical School,best known for her work in cell death. Early in her career,she contributed significant findings to the discovery and characterization of apoptosis. More recently,she was responsible for the discovery of the programmed form of necrotic cell death known as necroptosis.
Ced-3 is one of the major protein components of the programmed cell death (PCD) pathway for Caenorhabditis elegans. There are in total 14 genes that are involved in programmed cell death,other important ones including ced-4 and ced-9 genes. The healthy nematode worm will require 131 somatic cell deaths out of the 1090 cells during the developmental stages. The gene initially encodes for a prototypical caspase (procaspase) where the active cysteine residue cleaves aspartate residues,thus becoming a functional caspase. Ced-3 is an executioner caspase that must dimerize with itself and be initiated by ced-4 in order to become active. Once active,it will have a series of reactions that will ultimately lead to the apoptosis of targeted cells.
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