title: Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells.
abstract: TTRAP is a multi-functional protein that is involved in multiple aspects of cellular functions including cell proliferation, apoptosis and the repair of DNA damage. Here, we demonstrated that the lentivirus-mediated overexpression of TTRAP significantly inhibited cell growth and induced apoptosis in osteosarcoma cells. The ectopic TTRAP suppressed the growth and colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2. Cell apoptosis was induced in U2OS cells and the cell cycle was arrested at G2/M phase in Saos-2 cells. Exogenous expression of TTRAP in serum-starved U2OS and Saos-2 cells induced an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression. In comparison with wild-type TTRAP, mutations in the 5'-tyrosyl-DNA phosphodiesterase activity of TTRAP, in particular TTRAP(E152A), showed decreased inhibitory activity on cell growth. These results may aid in clarifying the physiological functions of TTRAP, especially its roles in the regulation of cell growth and tumorigenesis.
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Caihong
authors: C
authors: Zhou
authors: Qi
authors: Q
authors: Shen
authors: Jinglun
authors: J
authors: Xue
authors: Chaoneng
authors: C
authors: Ji
authors: Jinzhong
authors: J
authors: Chen
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000378:metabolism; D004268:DNA-Binding Proteins; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059566:M Phase Cell Cycle Checkpoints; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D056744:Cyclin B1; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D010727:Phosphoric Diester Hydrolases; C474866:TDP2 protein, human; C122147:tyrosyl-DNA phosphodiesterase; D053148:Caspase 3; D053179:Caspase 7