Guy Salvesen is a South African-born biochemist, best known for his work in the field of apoptosis. His research focuses on proteases and their inhibitors in humans, with particular emphasis on the caspases of the apoptotic cell death pathway.
Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the BIRC5 gene.
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.
Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present in birds.
Inhibitors of apoptosis are a group of proteins that mainly act on the intrinsic pathway that block programmed cell death, which can frequently lead to cancer or other effects for the cell if mutated or improperly regulated. Many of these inhibitors act to block caspases, a family of cysteine proteases that play an integral role in apoptosis. Some of these inhibitors include the Bcl-2 family, viral inhibitor crmA, and IAP's.
Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the CASP2 gene. CASP2 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.
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-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.
Baculoviral IAP repeat-containing protein3 is a protein that in humans is encoded by the BIRC3 gene.
Baculoviral IAP repeat-containing protein 2 is a protein that in humans is encoded by the BIRC2 gene.
Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene.
Calpain-2 catalytic subunit is a protein that in humans is encoded by the CAPN2 gene.
Diablo homolog (DIABLO) is a mitochondrial protein that in humans is encoded by the DIABLO gene on chromosome 12. DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC. This protein binds inhibitor of apoptosis proteins (IAPs), thus freeing caspases to activate apoptosis. Due to its proapoptotic function, SMAC is implicated in a broad spectrum of tumors, and small molecule SMAC mimetics have been developed to enhance current cancer treatments.
Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.
Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene. This protein is involved in caspase-dependent apoptosis and in Parkinson's disease.
Caspase 14 is an enzyme that in humans is encoded by the CASP14 gene.
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.
The protein Sf caspase-1 is the insect ortholog of the human effector caspases CASP3 (CPP32) and CASP7 (MCH3) in the species Spodoptera frugiperda. It was identified as the target of the baculoviral caspase inhibitor protein P35, which it cleaves and by which it is inhibited. Like other caspases, Sf caspase-1 is an aspartate-specific cysteine protease that is produced as an inactive proenzyme and becomes activated by autocatalytic cleavage. The Sf caspase-1 proenzyme is cleaved after the amino acid residues Asp-28 and Asp-195, resulting in a smaller 12 kDa fragment and a larger 19 kDa fragment. Just like with human caspases CASP3 or CASP7, the two cleavage fragments form heterodimers, which again form biologically active dimers-of-heterodimers consisting of two smaller and two larger fragments. Some experiments also showed cleavage of Sf caspase-1 at the residue Asp-184, resulting in an 18 kDa instead of 19 kDa fragment, however this result is likely an in vitro artefact. The insect immunophilin FKBP46 is a substrate of Sf caspase-1, which cleaves full length FKBP46 resulting in a ~25 kDa fragment.
Srinivasa Murty Srinivasula is an Indian cell biologist, a professor at the School of Biology at the Indian Institute of Science Education and Research, Thiruvananthapuram in Kerala, India. His research field is apoptosis, autophagy and oncology.
