Browse > Article
http://dx.doi.org/10.5483/BMBRep.2013.46.2.150

Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells  

Zhou, Caihong (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Shen, Qi (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Xue, Jinglun (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Ji, Chaoneng (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Chen, Jinzhong (State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University)
Publication Information
BMB Reports / v.46, no.2, 2013 , pp. 113-118 More about this Journal
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.
Keywords
Apoptosis, Growth inhibition, Osteosarcoma; TTRAP, Tyrosyl DNA phosphodiesterase;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Li, C., Fan, S., Owonikoko, T. K., Khuri, F. R., Sun, S. Y. and Li, R. (2011) Oncogenic role of EAPII in lung cancer development and its activation of the MAPK-ERK pathway. Oncogene 30, 3802-3812.   DOI   ScienceOn
2 Cortes Ledesma, F., El Khamisy, S. F., Zuma, M. C., Osborn, K. and Caldecott, K. W. (2009) A human 5'-tyrosyl DNA phosphodiesterase that repairs topoisomerase- mediated DNA damage. Nature 461, 674-678.   DOI   ScienceOn
3 Lee, B. H., Yoshimatsu, K., Maeda, A., Ochiai K., Morimatsu, M., Araki, K., Ogino, M., Morikawa, S. and Arikawa, J. (2003). Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules. Virus Res. 98, 83-91.   DOI   ScienceOn
4 Wang, B. Y., Xu, G. L., Zhou, C. H., Tian, L., Xue, J. L., Chen, J. Z. and Jia, W. (2010). PhiC31 integrase interacts with TTRAP and inhibits NF kappaB activation. Mol. Biol. Rep. 37, 2809-2816.   DOI
5 Zhang, J. Q., Wang, J. J., Li, W. J., Huang, L., Tian, L., Xue, J. L., Chen, J. Z. and Jia, W. (2009) Cellular protein TTRAP interacts with HIV-1 integrase to facilitate viral integration. Biochem. Biophys. Res. Commun. 387, 256-260.   DOI   ScienceOn
6 Xu, G. L., Pan, Y. K., Wang, B. Y., Huang, L., Tian, L., Xue, J. L., Chen, J. Z. and Jia, W. (2008) TTRAP is a novel PML nuclear bodies-associated protein. Biochem. Biophys. Res. Commun. 375, 395-398.   DOI   ScienceOn
7 Vilotti, S., Biagioli, M., Foti, R., Ferro, D. M., Lavina, S. Z., Collavin, L., Sal, D. G., Zucchelli, S. and Gustincich, S. (2012) The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition. Cell Death. Differ. 19, 488-500.   DOI   ScienceOn
8 Masuda, H., Miller, C., Koeffler, P. H., Battifora, H. and Cling, J. M. (1987) Rearrangement of the p53 gene in human osteogenic sarcomas. Proc. Natl. Acad. Sci. U.S.A. 84, 7716-7719.   DOI
9 Jensen, K., Shiels, C. and Freemont, P. S. (2001) PML protein isoforms and the RBCC/TRIM motif. Oncogene 20, 7223-7233.   DOI
10 Salomoni, P. and Khelifi, A. F. (2006) Daxx: death or survival protein? Trends Cell Biol. 16, 97-104.   DOI   ScienceOn
11 Varady, G., Sarkadi, B. and Fatyol, K. (2011) TTRAP is a novel component of the non-canonical TRAF6-TAK1 TGF-${\beta}$ signaling pathway. PLoS One 6, e25548.   DOI
12 Hanahan, D. and Weinberg, R. A. (2000) The hallmarks of cancer. Cell 100, 57-70.   DOI   ScienceOn
13 Li, C., Sun, S. Y., Khuri, F. R. and Li, R. (2011) Pleiotropic functions of EAPII/TTRAP/TDP2: cancer development, chemoresistance and beyond. Cell Cycle 10, 3274-3283.   DOI
14 Pype, S., Declercq, W., Ibrahimi, A., Michiels, C., Van Rietschoten, J. G., Dewulf, N., de Boer, M., Vandenabeele, P., Huylebroeck, D. and Remacle, J. E. (2000) TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor- 75 and TNF receptor-associated factors (TRAFs) and that inhibits nuclear factor-kappa B activation. J. Biol. Chem. 275, 18586-18593.   DOI   ScienceOn
15 Lee, H. Y., Youn, S. W., Kim, J. Y., Park, K. W., Hwang, C. I., Park, W. Y., Oh, B. H., Park, Y. B., Walsh, K., Seo, J. S. and Kim, H. S. (2008) FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB. Arterioscler. Thromb. Vasc. Biol. 28, 112-120.
16 Pei, H., Yordy, J. S., Leng, Q., Zhao, Q., Watson, D. K. and Li, R. (2003) EAPII interacts with ETS1 and modulates its transcriptional function. Oncogene 22, 2699-2709.   DOI   ScienceOn
17 Zhang, Z. B., Hu, J., Bi, Y. Y., Zhao, Z. W., Tao, N., Yan, H., Zhu, Z. L., Liu, Y. M. and Li, L. (2007) Effect of TTRAP expression on apoptosis induced by hydroquinone in HL-60 cells in vitro. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 25, 654-656.
18 Esguerra, C. V., Nelles, L., Vermeire, L., Ibrahimi, A., Crawford, A. D., Derua, R., Janssens, E., Waelkens, E., Carmeliet, P., Collen, D., Collen, D. and Huylebroeck, D. (2007) Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination. Development 134, 4381-4393.   DOI   ScienceOn
19 Zucchelli, S., Vilotti, S., Calligaris, R., Lavina, Z. S., Biagioli, M., Foti, R., De Maso, L., Pinto, M., Gorza, M., Speretta, E., Casseler, C., Tell, G., Del Sal, G. and Gustincich, S. (2009) Aggresome-forming TTRAP mediates pro-apoptotic properties of Parkinson's disease-associated DJ-1 missense mutations. Cell Death. Differ. 16, 428-438.   DOI   ScienceOn