title: Effect on apoptosis and cell cycle of recombinant double negative dominant mutation Survivin (T34/117A) in breast cancer cell B-Cap-37.
abstract: 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.
authors: Department of Gynaecology and Obstetrics, Tangshan Worker's Hospital, Tangshan 063000, China.
authors: Liqun
authors: L
authors: Wang
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors: Yanyan
authors: Y
authors: Kang
authors: School of Pharmacy and Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, China. Electronic address: zwy@ecust.edu.cn.
authors: Wenyun
authors: W
authors: Zheng
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors: Linfeng
authors: L
authors: Li
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors: Lei
authors: L
authors: Shi
authors: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors: Xingyuan
authors: X
authors: Ma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000494:pharmacology*; D064107:Aurora Kinase B / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C512124:HIV-TAT-survivin (T34A) protein; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus; C576921:AURKB protein, human; D064107:Aurora Kinase B; D053148:Caspase 3
keywords: Breast cancer cells; Cell cycle arrest; Pro-apoptosis; Survivin (T34/117A) mutant