p53 is one of the most important tumor suppressors, and one of its key functions is as a transcription factor by inducing the expression of a large number of p53 target genes to orchestrate complex biological activities. In cells, the activity of p53 is tightly regulated. p53 selective regulators have been demonstrated playing important role in p53 specific regulation. Recently, we identified Apak, a KZNF（KRAB-containing zinc finger protein）family member, as a specific negative regulator of p53-mediated apoptosis.
In my laboratory, we are interested to explore the selective regulation mechanisms of p53 and functional characterization of KZNF family members.
Current areas of emphasis include:
- Identifying and investigating p53 selective regulators from KZNF family.
- Selective regulation mechanism of p53.
- Function and mechanism study of KZNF family members.
A combined approach of molecular and cellular biology, proteomics and gene knockout mouse models will be used in our studies.
1. Lin Yuan#, Chunyan Tian#, Hongye Wang, Shanshan Song, Deyang Li, Guichun Xing, YuxinYin, Fuchu He, Lingqiang Zhang. Apak competes with p53 to bind directly to p53AIP1 intron to regulate apoptosis. EMBO Reports. 2012, 13(4): 363-70. (#co-first authors)
2. Jing Nie, Ping Xie, Lin Liu, Guichun Xing, Zhijie Chang, Yuxin Yin, Chunyan Tian*, Fuchu He*, Lingqiang Zhang*. Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by stabilizing the E3 ligase MDM2. J Biol Chem. 2010, 285(30): 22818-30. (#corresponding authors)
3. Jing Nie, Lin Liu, Min Wu, Guichun Xing, Shan He, Yuxin Yin, Chunyan Tian*, Fuchu He*, Lingqiang Zhang*. HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation. FEBS Lett. 2010, 584(14): 3005-12. (#corresponding authors)
4. Chunyan Tian, Guichun Xing, Ping Xie, Kefeng Lu, Jing Nie, Jian Wang, Li Li, Mei Gao, Mei Gao, Lingqiang Zhang*, Fuchu He*. KRAB type zinc finger protein Apak specifically regulates p53-dependent apoptosis. Nature Cell Biology，2009, 11(5): 580-591.
5. Ping Xie, Chunyan Tian*, Liguo An, Jing Nie, Kefeng Lu, Guichun Xing, Lingqiang Zhang*, Fuchu He*. Histone methyltransferase protein SETD2 interacts with p53 and selectively regulates its downstream genes. Cell. Signal. 2008, 20(9): 1671-1678. (#)
6. Yanzhi Yuan, Chunyan Tian, Qiaoling Gong, Limin Shang , Yuehui Zhang Y, Chaozhi Jin, Fuchu He, Jian Wang. Interactome Map Reveals Phospholipid Scramblase 1 as a Novel Regulator of Hepatitis B Virus X Protein. J Proteome Res. 2015, 14(1):154-63.
7. Dong Yang, Zhanfu Ma, Weiran Lin, Juntao Yang, Chunyan Tian, Handong Wei, Ying Jiang, Fuchu He. Identification of KAP-1-associated complexes negatively regulating the Ey and β-major globin genes in the β-globin locus. J Proteomics. 2013, 80C: 132-144.
8. Shukuan Ling, Qiao Sun, Yuheng Li, Luo Zhang, Pengfei Zhang, Xiaogang Wang, Chunyan Tian, Qi Li, Jinping Song, Hongju Liu, Guanghan Kan, Hongqing Cao, Zengming Huang, Jielin Nie, Yanqiang Bai, Shanguang Chen, Yinghui Li, Fuchu He, Lingqiang Zhang and Yingxian Li. CKIP-1 Inhibits Cardiac Hypertrophy by Regulating Class II Histone Deacetylase Phosphorylation through Recruiting PP2A. Circulation. 2012, 126(25): 3028-3040
9. Li Li, Binwei Deng, Guichun Xing, Yan Teng, Chunyan Tian, Xuan Cheng, Xiushan Yin, JuntaoYang, Xue Gao, Yunping Zhu, Lingqiang Zhang#, Xiao Yang#, Fuchu He#. PACT is a negative regulator of p53 and essential for cell growth and embryonic development. PNAS. 2007, 104(19), 7951-7956.
(# co-first authors, * corresponding authors)