Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin.

ABSTRACT: Survivin is a member of the inhibitor of apoptosis protein family and has an essential role in mitosis. Survivin is overexpressed in a large variety of human cancers and represents an attractive target for cancer therapy. Epidermal growth factor receptor and Her/neu-transformed human tumors in particular exhibit high levels of survivin. The survivin protein forms dimers through a conserved region that is critical for subcellular localization and biological functions of the protein. We identified small molecules that target a specific cavity adjacent to the survivin dimerization surfaces. S12, a lead compound identified in the screen, can bind to the survivin protein at the intended target site. Moreover, S12 alters spindle formation, causing mitotic arrest and cell death, and inhibits tumo

SUBMITTER: Berezov A 

PROVIDER: S-EPMC3570121 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature