An IAP in action: the multiple roles of survivin in differentiation, immunity and malignancy.
The proteolytic activity of caspases is tightly controlled by the inhibitor of apoptosis protein (IAP) family that has evolved to protect cells from unwanted self-execution by fortuitous activation of the death cascade. Survivin is a 17 kD protein that contains only a single BIR and no RING domain. It stands out for its close association with cancer where its expression correlates with drug resistance and poor prognosis. In the nucleus, survivin binds to microtubules and assists in chromosomal segregation and cytokinesis during mitosis. In the cytoplasm, survivin inhibits apoptosis by interacting with caspase-9 in the presence of the HBXIP cofactor, by binding to Smac or associating with XIAP. Recent data demonstrate that survivin is also expressed in normal proliferating hematopoietic cells as well as in terminally differentiated neutrophils, where it, following upregulation by hematopoietic growth factors, inhibits apoptosis independent of the cell cycle.
Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
Uwe
U
Zangemeister-Wittke
Hans-Uwe
HU
Simon
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007109:Immunity / Q000502:physiology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D020169:Caspases