Effect on apoptosis and cell cycle of recombinant double negative dominant mutation Survivin (T34/117A) in breast cancer cell B-Cap-37

As a bi-functional molecule in anti-apoptosis and pro-proliferation, Survivin is considered to be an attractive target for anti-cancer drug development all the time. Some studies show that these effects of survivin are mainly from two phosphorylation sites on its different domain, Thr 34 and Thr117, but it remains unclear that how they involve respectively in the apoptosis and the cell cycle of cancer cells, hindering the design and preparation of novel anti-cancer drug target to survivin. In the study, a series of recombinant double negative dominant mutants of survivin were constructed, expressed and purified efficiently, and their effects on cell cycle and apoptosis of breast cancer cell B-Cap-37 were investigated. The results showed that Survivin Thr117 is a key site on regulation of proliferation and cycle by Aurora B kinase phosphorylation, and Survivin Thr34 involves cell apoptosis by decreasing mitochondria membrane potential (MMP) and activating caspase-3. Further studies have also shown that recombinant double negative dominant mutation Survivin (T34/117A) could significantly inhibit the proliferation of B-Cap-37 cells and arrest cell in G0/G1 phase and G2/M phase, indicating the double mutant is a more potential candidate as anti-cancer drug.