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Xiongbin LuAssistant Professor of Biological Sciences
Office & Lab: CLS 608
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Xiongbin LuAssistant Professor of Biological Sciences
Office & Lab: CLS 608
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Among many ATM/ATR targets, p53 (encoded by TP53 gene) is a transcription factor and serves as a pivotal tumor suppressor in animals. More than 50 percent of human tumors contain a mutation or deletion of the TP53 gene. The p53 tumor suppressor directs a transcriptional program that prevents the proliferation of genetically unstable cells. Inappropriate regulation of p53 results in a severed consequence for cells. While the loss of p53 function predisposes cells to tumorigenesis, errant p53 activation can lead to premature senescence or apoptosis. The primary homeostatic regulation of p53 is through Mdm2-mediated proteosomal degradation. Upon DNA damage stress, p53 not only transcriptionally regulates genes involved in cell cycle arrest or apoptosis, but also its own negative regulator, Mdm2. Thus, p53 and Mdm2 participate in an auto-regulatory feedback loop.
My laboratory is interested in identifying and understanding homeostatic regulators that regulate DNA damage checkpoints and p53 activities. Current areas of emphasis include: (1) biological functions of the oncogenic Wip1 phosphatase in tumor progression; (2) regulation of protein phosphatases in the p53-Mdm2 auto-regulatory feedback loop; (3) stabilization of p53 through inhibiting Mdm2 and its interaction with p53. A combined approach of proteomics, genomics and mouse cancer models will be used in our studies.
Lu, X.*, Ma, O., Nguyen, T., Jones, S.N., Oren, M., Donehower, L. A.* (2007). The Wip1 phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell, in press (* co-corresponding authors).
Nannenga, B., Lu, X., Dumble, M., Van Maanen, M., Nguyen, T., Kittrell, F., Medina, D., Kumar, R., Donehower, L. A. (2006). Augmented cancer resistance and DNA damage response phenotypes in Wip1 null mice. Molecular Carcinogenesis, 45(8): 594-604 (featured as cover story).
Adams, M. M., Wang, B., Xia, Z., Morales, J.C., Lu, X., Donehower, L.A., Bochar D. A., Elledge, S. J., Carpenter, P. B. (2005) 53BP1 oligomerization is independent of its methylation by PRMT1. Cell cycle, 4(12): 1854-61.
Lu, X., Nguyen, T., Appella, E., Donehower, L.A. (2005). Reversal of the ATM/ATR-Mediated DNA Damage Response by the Oncogenic Phosphatase PPM1D. Cell Cycle, 4(8): 1060-1064.
Lu, X., Nannenga, B., Donehower, L.A. (2005). PPM1D dephosphorylates CHK1 and p53 and abrogates cell cycle checkpoints. Genes & Development, 19(10): 1162-74 (profiled in Nature Reviews Cancer, 5(6):416).
Lu, X., Nguyen, T., Appella, E., Donehower, L.A. (2004). Homeostatic regulation of base excision repair by a p53-induced phosphatase: Link stress response pathways with DNA repair proteins. Cell Cycle, 3(11): 1363-1366.
Lu, X., Bocangel, D., Nannenga, B., Yamaguchi, H., Appella, E., Donehower, L. A. (2004). The p53-Induced Oncogenic Phosphatase PPM1D Interacts with Uracil DNA Glycosylase and Suppresses Base Excision Repair. Molecular Cell, 15(4): 621-34.
Dumble, M. L., Donehower, L. A., Lu, X. (2003). Generation and characterization of p53 mutant mice. Methods in Molecular Medicine, 234: 29-49.
Lu, X., Lozano, G., Donehower, L. A. (2003). Activities of wildtype and mutant p53 in suppression of homologous recombination as measured by a retroviral vector system. Mutation Research, 522(1-2): 69-83.
Lu, X., Xiong, Y., Silver, J. (2002). Asymmetric requirement for cholesterol in receptor- bearing but not envelope-bearing membranes for fusion mediated by ecotropic murine leukemia virus. Journal of Virology, 76(13): 6701-9.
Tyner, S., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., Karsenty, G., Bradley, A., Donehower, L. A. (2002), A germline p53 mutation associated with enhanced resistance and altered longevity in mice. Nature, 415(6867): 45-53.
Lu, X. and Silver, J. (2001). Transmission of replication-defective Sindbis helper vectors encoding capsid and envelope proteins. Journal of Virological Methods, 91(1): 59-65.
Silver, J., Lu, X. (2001). Semliki Forest Virus, Wiley Encyclopedia of Molecular Medicine, John Wiley and Sons, Inc., Volume 5, 2888-2890.
Lu, X. and Silver, J. (2000). Ecotropic murine leukemia virus receptor is physically associated with caveolin and membrane rafts. Virology, 276(2): 251-8 (featured as cover story).