What is Survivin in cancer?
Survivin, an inhibitor of apoptosis protein, is highly expressed in most cancers and associated with chemotherapy resistance, increased tumor recurrence, and shorter patient survival, making antisurvivin therapy an attractive cancer treatment strategy.
What does Survivin do?
Survivin is the smallest member of the Inhibitor of apoptosis (IAP) family of proteins, involved in inhibition of apoptosis and regulation of cell cycle. These functional attributes make Survivin a unique protein exhibiting divergent functions i.e. regulating cell proliferation and cell death.
Is survivin an oncogene?
Survivin can be regarded as an oncogene as its aberrant overexpression in most cancer cells contributes to their resistance to apoptotic stimuli and chemotherapeutic therapies, thus contributing to their ongoing survival.
What do executioner caspases do?
Initiator caspases initiate the apoptosis signal while the executioner caspases carry out the mass proteolysis that leads to apoptosis. Inflammatory caspases do not function in apoptosis but are rather involved in inflammatory cytokine signaling and other types of cell death such as pyroptosis.
How are executioner caspases activated?
The executioner caspases are zymogens that are activated by upstream initiator caspases such as caspase-8 and caspase-9. After proteolytic cleavage, the large (α) and small (β) subunits assemble into catalytically active oligomers, with αββ′α′ symmetry, that have two active sites per complex.
What happens when caspase is cleaved?
Cleavage. Once appropriately dimerised, the Caspases cleave at inter domain linker regions, forming a large and small subunit. This cleavage allows the active-site loops to take up a conformation favourable for enzymatic activity.
What effect do caspases have?
Effector caspases are responsible for initiating the hallmarks of the degradation phase of apoptosis, including DNA fragmentation, cell shrinkage and membrane blebbing [8, 9].