Protein Degradation Research Laboratory
Dean of the Biochemistry and Molecular Biology division
Dr. Xiaotao Li received his M.D. Degree from Chongqing University of Medical Sciences in 1989. After a few years of clinical practice, he matriculated to the United State and obtained his Ph.D. Degree in Biochemistry and Molecular Biology at the University of Texas MD Anderson Cancer Center in 2001. Upon his completion of postdoctoral training, he was promoted to Instructor and then Assistant Professor at Baylor College of Medicine during 2005-2007. He was a recipient of National Research Science Award and NIH R01 grant and had 25 publications in numerous high impact journals with over 700 citations. He pioneered with his former mentor, Dr. Bert O'Malley, in the discovery of the first mammalian target of REGγ (a proteasome activator) complex, which mediates ubiqutin-independent shortcut for protein destruction (Cell, 2006). The biological significance of the REGγ-proteasome pathway was established with subsequent endeavor (Mol. Cell 2006). Soon after his return to China, he dedicated to intensive and extensive analysis of this protein degradation pathway with the support from, National Natural Science Foundation, and the Ministry of Science and Technolo Shanghai Educational Department, Science and Technology Commission of Shanghai Municipality gy of China. Dr. Li is now a Professor at the School of Life Sciences-East China Normal University and the Dean of the Biochemistry and Molecular Biology division.
Dr. Li lead a research team focusing on the protein degradation pathway mediated by the REGγ- proteasome following his initial discovery of a couple of REGγ targets. The long term goal of this team is to extensively understand the biological actions of the REGγ- proteasome and its pathological roles in various human diseases when functions anomaly. Currently, progress are made in the identification of REGγ substrates including p53 (JCS， 2010； J Virology， 2010), regulation of REGγ activity by post-translational modification (Cell Res， 2011), as well as correlation between REGγ and multiple carcinogenic signaling (BMC Cancer 2012). Our efforts are empowering this field as a promising research area, though it's just a beginning. To address further scientific questions in more details, we have initiated various projects using REGγ deficient animal models, revealing the involvement of REGγ-proteasome in multiple biological processes such as neuronal functions, male reproduction, auto-immunity, metabolism, autophagy, aging and cancer progression.
1. Jing He, Long Cui, Yu Zeng, Guangqiang Wang, Li X*. (2012). REGgamma is associated with multiple oncogenic pathways in human cancers. BMC Cancer. Feb 23; 12(1):75
2. Qiao S, Murakami K, Zhao Q, Wang B, Seo H, Yamashita H, Li X, Iwamoto T, Ichihara M, Yoshino M. (2012). Mimosine-Induced Apoptosis in C6 Glioma Cells Requires the Release of Mitochondria-Derived Reactive Oxygen Species and p38, JNK Activation. Neurochem Res. Feb;37(2):417-27.
3. Shen J, Zhang S, Li Y, Zhang W, Chen J, Zhang M, Wang T, Jiang L, Zou X, Wong J, Li X, Cui Y, Wang C. (2011). p14(ARF) inhibits the functions of adenovirus E1A oncoprotein. Biochem J. Mar 1;434(2):275-85.
4. Wu Y, Wang L, Zhou P, Wang G, Li X*. (2011). Regulation of REGg cellular distribution and function by SUMO modification. Cell Research. 2011 May; 21(5):807-16.
5. Gao G, Wong J, Zhang J, Mao I, Shravah J, Wu Y, Xiao A, Li X*, Luo H. (2010). Proteasome Activator REGg Enhances Coxsackieviral Infection via Facilitating p53 Degradation. J. Virol. 84 (21): 11056-11066.
6. Liu J, Yu G., Zhao P., Wang C., Luo H., Long W., Wang Y., Zhao Y., Tsai M., O'Malley B.W. and Li X*. (2010). REGγ modulates p53 activity by regulating its cellular localization. J. Cell Science. 123 (pt23): 4076-84.
7. Tian M, Xiaoyi W, Li X, Guosheng R. (2009). Proteasomes reactivator REGgamma enchances oncogenicity of MDA-MB-231 cell line via promoting cell proliferation and inhibiting apoptosis. Cell Mol Biol (Noisy-le-grand). 55 Suppl:OL1121-31.
8. Yu G, Zhao Y, He J, Mukherjee A, Mao CA, Li M, and Li X*. (2008). Comparative analysis of REGγ expression augurs functional implication. J. Mol. Cell. Biol. Aug; 2(4):192-8.
9. Ivy Mao, Jian Liu, Li X*, Honglin Luo. (2008). REGg, A Proteasome Activator and Beyond? Cell and Mol Life Sci. Dec;65(24):3971-80.
10. Li X, Larbi Amazit, Weiweng Long, David M. Lonard, John J. Monaco and
11. O’Malley B.W. (2007). Proteolytic turnover of p21 by the REGgamma-proteasome pathway. Mol. Cell, 26, 831-842
12. Li X., Lonard D., Jung S.Y., Malovannaya A., Feng Q., Qin J., Tsai S. Y., Tsai M-J., and O’Malley B.W. (2006). The SRC-3/AIB1 coactivator is degraded in an ubiquitin- and ATP-independent manner by the REGgamm-proteasome Cell. 124, 381-392.
13. Verma S., Ismail A., Gao X., Fu G., Li X., O’Malley B. W., Nawaz Z. (2004). Ubiquitin-conjugating enzyme, UBCH7 act as a coactivator for steroid hormone receptors. Mol. Cell. Biol. 24, 8716-26.
14. Li X. Lonard D. M. and O’Malley B. W. (2004). A Contemporary Understanding of Progesterone Receptor Function (Review). Mechanisms of Aging and Development. 125, 669-78.
15. Auboeuf D., Dowhan D.H., Li X., Larkin K., Ko L., Berget S.M., O'Malley B.W. (2004). CoAA, a Nuclear Receptor Coactivator Protein at the Interface of Transcriptional Coactivation and RNA Splicing. Mol. Cell. Biol. 24, 442-53.
16. Li X. and O'Malley B.W. Unfolding the action of progesterone receptors (minireview). (2003). J. Biol. Chem. 10, 39261-4.
17. Li X., Wong J., Tsai S.Y., Tsai M.J., and O'Malley B.W. (2003). Progesterone and glucocorticoid receptors recruit distinct coactivator complexes and promote distinct patterns of local chromatin modification. Mol. Cell. Biol. 23, 3763-73.
18. Li X., Bhattacharya C., Maity S., Dayal S, and Klein W.H. (2002). Ectoderm Gene Activation in Sea Urchin Embryos Mediated by CCAAT Binding Factor CBF. Differentiation. 70, 109-19
19. Angerer L.M., Oleksyn D. W., Levine A.M., Li X., Klein W.H. and Angerer R. (2001). Sea urchin goosecoid function links fate specification along the animal-vegetal and oral-aboral embryonic axes. Development. 128, 4393-404
20. Yuh C., Li X., Davidson E.H., and Klein W.H. (2001). Correct Expression of Spec2a in the Sea Urchin Embryo Requires Both Otx and Other cis-Regulatory Elements. Dev. Biol. 232, 424-438
21. Huang L., Li X., El-Hodiri H.M., Dayal S., Athula H.W., and Klein W.H. (2000). Involvement of Tcf/Lef in Establishing Cell Types along the Animal-Vegetal Axis of Sea Urchins. Dev. Genes Evol. 210, 73-81.
22. Li X., Athula HW and Klein WH. (1999). Requirement of SpOtx in Cell Fate Decisions in the Sea Urchin Embryo and Possible Roles as a Mediator of beta-Catenin Signaling. Dev. Biol. 212, 425-439
23. Klein W.H. and Li X. (1998). Function and Evolution of Otx Proteins. Biochem. Biophys. Res. Commun. 258, 22-34
24. Li X., Chuang C.K., Mao C.A., Angerer L.M., and Klein WH. (1997). Two Otx proteins generated from alternative splicing of multiple transcripts of a single gene in Strongylocentrotus purppuratus. Dev. Biol. 187, 253-266
25. Chuang C.K., Athula H.W., Mao C.A., Li X. and Klein W.H. (1996). Transient Appearance of S. purpuratus Otx in Micromere Nuclei: Cytoplasmic Retention of SpOtx Mediated Through an alpha-Actinin SH3 Domain. Dev. Genetics 19, 231-239
26. Li X., Weinstock G.M. and Murray B.E. (1995). Generation of Auxotrophic mutants of Enterococcus faecalis. J. Bacteriol. 177, 6866-6873