Figure 2.

Pathways through which survivin can favor tumor cell development. Survivin is a component of the chromosome passenger complex (CPC) and a key regulator of chromosome segregation and cytokinesis. The association of survivin with two other components of the CPC complex, INCENP (inner centromere protein antigen) and borealin, regulate the localization of the aurora kinase B enzymatic component, to kinetochores. Aurora kinase B undergoes auto-phosphorylation upon recruitment to the CPC complex, promoting correct chromosome alignment, segregation and cytokinesis during mitosis. In addition, DNA damage-induced activation of checkpoint kinase 2 (Chk2) results in rapid release of survivin from mitochondria, inhibiting cell death and promoting tumor cell survival. DNA damage also stabilizes wild-type p53, repressing the transcription of survivin and helping to balance this pathway.