Ubiquitin-mediated protein degradation plays an important and wide role in various cellular processes. Abnormal protein ubiquitination and degradation result in human diseases including human cancer and osteoporosis.
Our group are interested with the function, regulation and disease relevance of the key regulators in protein ubiquitination and degradation, such as ubiquitin E3 ligases, deubiquitinases and the ligases for ubiquitin-like protein Nedd8. We are aiming to identify the key players in the initiation and progression of human cancer and investigate the molecular mechanisms. To this end, we have generated and will continue generating a series of gene knockout mice models. On the other hand, we will deepen our understandings of how the osteoporosis occur accompanied with ageing or loss of agravity and how to treat the osteoporosis based on promoting the bone formation rather than antagonizing the bone resorption alone.
1． Lin Yuan et al, Deubiquitinase OTUD3 regulates PTEN stability and suppresses tumorigenesis. Nature Cell Biology, 2015, 17(9): 1169-1181.
2． Chunyan Tian et al, KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis. Nature Cell Biology, 2009, 11(5): 580-591.
3． Kefeng Lu et al, Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1. Nature Cell Biology, 2008, 10(8): 994-1002.
4． Chao Liang et al, Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. Nature Medicine, 2015, 21(3): 288-294.
5． Ge Zhang et al, A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nature Medicine, 2012, 18(2): 307-314.
6． Ping Xie et al, Covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nature Communications, 2014, 5: 3733.
7． Shukuan Ling et al, CKIP-1 inhibits cardiac hypertrophy by regulating class II histone deacetylase phosphorylation through recruiting PP2A. Circulation, 2012, 126(25): 3028-3040.
8． Luo Zhang et al, CKIP-1 regulates macrophage proliferation by inhibiting TRAF6-mediated Akt activation. Cell Research, 2014, 24(6): 742-761.
9． Shanshan Song et al, N-Methylpurine DNA glycosylase (MPG) inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents. Cell Research, 2012, 22(8): 1285-1303.
10． Yu Cui et al, SCFFBXL15 regulates BMP signaling by directing the degradation of HECT-type ubiquitin ligase Smurf1. EMBO Journal, 2011, 30(13): 2675-2689.