Personal History1986: B.S. in Biology, Peking University, Beijing, P. R. China.
1990: M.S. in Biology, Peking University, Beijing, P. R. China.
1999: Ph.D. in Biology, University of Kentucky, Lexington, KY 40506
1999-2002: Post-doctoral Fellow, Columbia University, NYC
Research InterestsCancer is a disease of aging and is increasing in magnitude as people live longer. Certain genetic and epigenetic alterations are accumulated during aging and appear to possess a direct role in cell transformation. The levels of NAD-dependent Class III histone deacetylase SIRT1 has been shown to be decreased during aging and elevated in cancer cells. It is being increasingly appreciated that SIRT1 could be one of the links between aging and cancer. SIRT1 is a multiple functional protein related to cancer and aging and it has been demonstrated critically involved in stress response, cellular metabolism and tumorigenesis through deacetylating variety of substrates. The research in Luo lab is focus on SIRT1 regulating protein functions in mammalian aging and cancer. Currently, Luo lab has established several distinguish projects studying aging and cancer through protein acetylation and deacetylation pathway. The first project is regulation of WRN function by SIRT1-mediated deacetylation after DNA damage. Werner syndrome is an autosomal recessive disorder associated with pre-mature aging and cancer predisposition caused by mutations of the WRN gene. WRN is a member of the RecQ DNA helicase family with functions in DNA replication, recombination and repair. SIRT1 interacts with WRN and the interaction is enhanced after DNA damage. WRN is acetylated by CBP/p300 and SIRT1 deacetylates WRN. WRN acetylation decreases its helicase and exonuclease activities and SIRT1 can reverse this effect. WRN acetylation alters its nuclear distribution. Six lysine residues in WRN has been identified as major acetylation sites. WRN acetylation increases its protein stability. SIRT1-mediated deacetylation of WRN reverses this effect. WRN stability is regulated by the ubiquitination pathway and WRN acetylation by CBP significantly reduces its ubiquitination. The second project in Luo lab is study Rothmund-Thomson syndrome responsive gene RecQ4 functions and its regulation by SIRT1. RecQ4 is another member of a RecQ DNA helicase family. Luo lab has found that SIRT1-mediated deacetylation can regulate RecQ4 function in DNA replication. In another direction, they also found that RecQ4 facilitates UV-induced DNA damage repair through interaction with nucleotide excision repair factor XPA. The third project in Luo lab is regulation of XPA function by acetylation and SIRT1 mediated deacetylation. In addition, Luo lab also work on regulation of Stat3 function by reversible acetylation and SIRT1 in cancer.
Guo, A., Salomoni, P., Luo, J., Shih, A., Zhong, S., Gu, W., Pandolfi, P. (2000). The function of PML in p53-dependent apoptosis. Nat Cell Biol 2, 730-736.
Luo, J., Su, F., Chen, D., Shiloh, A., Gu, W. (2000). Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408, 377-381. (Highlight: Nature Reviews Molecular Cell Biology 1, 164)
Luo, J., Nikolaev, A., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L., Gu, W. (2001). Negative control of p53 by Sir2[alpha] promotes cell survival under stress. Cell 107, 137-148.
Li, M., Chen, D., Shiloh, A., Luo, J., Nikolaev, A., Qin, J., Gu, W. (2002) Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature 416, 648-653.
Li, M., Luo, J., Brooks, C., Gu, W. (2002) Acetylation of p53 inhibits its ubiquitination by mdm2. J Biol. Chem. 277, 50607-50611.
Chen, D., Li, M., Luo, J., Gu, W. (2003) Direct interactions between HIF-1Î± and Mdm2 induce p53 stabilization. J Biol. Chem. 278, 13595-13598.
Luo, J., Li, M., Tang, Y., Laszkowska, M., Roeder, B., Gu, W (2004) Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc. Natl. Acad. Sci. USA 101, 2259-2264. published February 12, 2004, 10.1073/pnas.0308762101.
Chen W.Y., Wang, D. H., Yen, R. C., Luo, J., Gu, W., Baylin, S. B. (2005) Tumor Suppressor HIC1 Directly Regulates SIRT1 to Modulate p53-Dependent DNA-Damage Responses. Cell 123, 437-448.
Wang, R., Cherukuri, P., Luo, J. (2005) Activation of Stat3 sequence-specific DNA binding and transcription by p300/CBP mediated acetylation. J Biol. Chem. 280, 11528-11534.
Wang, Y., Oh, S. W., Deplancke, B., Luo, J., Walhout, A. J. M. and Tissenbaum, H. A. (2006) C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech Ageing and Dev, 127, 741-747.
Tang, Y., Luo, J., Zhang, W., Gu, W. (2006) Tip60-dependent acetylation of p53 modulates the decision between cell cycle arrest and apoptosis. Mol. Cell, 24, 827-839.
Sekaric, P., Shamanin, V.A., Luo, J., Androphy, E. J. (2007) hAda3 regulates p14ARF-induced p53 acetylation and senescence. Oncogene, 26, 6261-6268.
Bordone, L., Cohen1, D., Robinson, A., Motta, MC.,1, van Veen, E., Czopik, A., Steele, A., Crowe, H., Marmor, S., Luo, J., Gu, W., Guarente, L. (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell. 6, 759-767.
Li, K., Casta, A., Wang, R., Lozada, E., Fan, W., Kane, S., Ge, Q., Gu, W., Orren, D., Luo, J. (2008) Regulation of WRN protein cellular localization and enzymatic activities by SIRT1 mediated deacetylation. J Biol. Chem. 283, 7590-7598.
Fan, W., & Luo, J. (2008) RecQ4 facilitates UV-induced DNA damage repair through interaction with nucleotide excision repair factor XPA. J Biol. Chem. 283, 29037-29044. published August 7, 2008 as doi:10.1074/jbc.M801928200.
Luo, J., & Altieri, D. C. (2008) SIRTing through breast cancer is just a Surviving game. Mol. Cell, 32, 159-160. (Co-corresponding Author).
Li, K., Wang, R., Lozada, E., Fan, W., Orren, D., Luo, J. (2010) Acetylation of WRN protein regulates its stability by inhibiting ubiquitination. PLoS One, 5, e10341.
Yi, J., & Luo, J. (2010) SIRT1 and p53, effect on cancer, senescence and beyond. Biochim Biophys Acta. 1804, 1684-1689.
Fan, W., & Luo, J. (2010) SIRT1 regulates UV-induced DNA repair through deacetylating XPA. Mol. Cell, 39, 247-258.
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