Survivin [D8]

Survivin is a unique member of the inhibitor of apoptosis (IAP) protein family that interferes with post-mitochondrial events, including activation of caspases. Survivin regulates the cell cycle and is expressed in most tumors, but it is barely detectable in terminally differentiated normal cells and tissues. Survivin is expressed in the G2/M phase of the cell cycle. At the beginning of mitosis, survivin associates with microtubules of the mitotic spindle in a specific and saturable reaction that is regulated by microtubule dynamics. Disruption of survivin-microtubule interactions results in loss of survivin’s anti-apoptotic function and increased caspase-3 activity, a mechanism involved in cell death during mitosis. Nuclear-cytoplasmic shuttling of survivin is controlled by nuclear export signal (NES), which is necessary for the anti-apoptotic function of survivin. Inhibition of the NES makes cells more susceptible to chemotherapy- or radiotherapy-induced apoptosis. The association of survivin expression with tumor progression, but not overall patient survival, has been observed in a variety of malignancies including renal cell carcinoma, ovarian carcinoma, hepatocellular carcinoma, prostate carcinoma and breast carcinoma. However, the link between a poor prognosis and nuclear expression of Survivin in tumors is controversial. A literature review of 19 publications that measured nuclear survivin in different cancer types showed the following: 9 studies concluded that nuclear survivin was associated with an unfavorable prognosis, whereas 5 showed a favorable prognosis. The authors concluded that the nuclear pool of survivin is involved in promoting cell proliferation in most (if not all) cases, whereas the cytoplasmic pool of survivin may participate in controlling cell survival but not cell proliferation.