Zangemeister-Wittke Uwe, Simon Hans-Uwe
Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
Cell Cycle. 2004 Sep;3(9):1121-3. Epub 2004 Sep 15.
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.
半胱天冬酶的蛋白水解活性受到凋亡抑制蛋白（IAP）家族的严格控制，IAP家族的进化是为了保护细胞避免因死亡级联反应的意外激活而进行不必要的自我执行。存活素是一种17kD的蛋白质，仅含有一个BIR结构域且无RING结构域。它因与癌症密切相关而引人注目，其表达与耐药性和不良预后相关。在细胞核中，存活素与微管结合，并在有丝分裂期间协助染色体分离和胞质分裂。在细胞质中，存活素在HBXIP辅助因子存在的情况下通过与半胱天冬酶-9相互作用、与Smac结合或与XIAP缔合来抑制细胞凋亡。最近的数据表明，存活素也在正常增殖的造血细胞以及终末分化的中性粒细胞中表达，在这些细胞中，它在造血生长因子上调后，独立于细胞周期抑制细胞凋亡。
