本实验室主要兴趣在于：
转录因子NF-κB活化的细胞内信号途径及调控机制
NF-κB（nuclear factor-κB）是在各种类型细胞中广泛表达的重要转录因子。通常与抑制因子IκBs（inhibit κB）相结合，以非活性形式存在于细胞质中。在外界刺激因素如病原体感染、肿瘤或癌症诱导剂等的作用下，NF-κB被激活，启动大量与细胞应急状态相关的基因的转录，导致多种细胞生理效应，如：固有免疫及获得性免疫应答，炎症反应，促进细胞增殖及永生化等。NF-κB必须适度活化才对人体有利。活化不足会造成人体对各种病原体的免疫缺陷，而过度活化则会导致肿瘤及风湿性关节炎等疾病。我们运用酵母双杂交（Yeast Two-hybrid Screening System）等细胞及分子生物学手段，克隆NF-κB活化相关信号通路中的关键性信号分子和调节因子。研究成果将有助于阐明信号转导的分子机制，同时能够为相关疾病的治疗提供药物设计靶标。
Research Description:
NF-κB is a ubiquitously expressed transcription factor that is normally sequestered by inhibitory proteins IκBs in the cytoplasm. NF-κB is activated by divergent stimuli, such as microbial pathogens, carcinogens and tumor promoters. Activated NF-κB regulates the expression of a large number of genes, including those involved in innate and adaptive immune responses, inflammatory responses, cellular transformation and proliferation. De-regulation of NF-κB is involved in a wide range of human diseases, such as immune deficiency, rheumatoid arthritis and cancer. We take cellular and molecular approaches to identify signaling proteins and regulatory proteins that critically involved in NF-κB activation pathways. We hope to contribute to understanding of the signaling mechanisms and may also suggest new targets for drugs development
代表性论文
1. Li MT, Di W, Xu H, Yang YK, Chen HW, Zhang FX, Zhai ZH, Chen DY , Negative regulation of RIG-I-mediated innate antiviral signaling by SEC14L1. , J Virol. , 2013 , 18:10037-46
2. Yang YK, Qu H, Gao D, Di W, Chen HW, Guo X, Zhai ZH, Chen DY. , ARF-like protein 16 (ARL16) inhibits RIG-I by binding with its C-terminal domain in a GTP-dependent manner. , J Biol Chem. , 2011 , 286:10568–10580.
3. Gao D, Wang R, Li B, Yang Y, Zhai Z, Chen DY. , WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway. , Cell Mol Life Sci. , 2009 , 6615:2573-84.
4. Gao D, Yang YK, Wang RP, Zhou X, Diao FC, Li MD, Zhai ZH, Jiang ZF, Chen DY. , REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. , PLoS ONE , 2009 , 4(6):e5760.
5. Chen F, Du YJ, Chen G, Zhang Z, Zhang M, Shu HB, Zhai Z, Chen D , Syntenin negatively regulates TRAF6-mediated IL-1R/TLR4 signaling. , Cell Signal , 2008 , 20:666-674
6. Zhang M, Tian Y, Wang RP, Gao D, Zhang Y, Diao FC, Chen DY, Zhai ZH, Shu HB. , Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3. , Cell Res. , 2008 , 18:1096-1104.
7. Diao F, Li S, Tian Y, Zhang M, Xu LG, Zhang Y, Wang RP, Chen D, Zhai Z, Zhong B, Tien P, Shu HB , Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase. , Proc Natl Acad Sci U S A , 2007 , 104:11706-11711.
8. Wang RP, Zhang M, Li Y, Diao FC, Chen D, Zhai Z, Shu HB , Differential regulation of IKKalpha-mediated activation of IRF3/7 by NIK. , Mol Immunol. , 2007 , 45:1926-1934
9. Tian Y, Zhang Y, Zhong B, Wang YY, Diao FC, Wang RP, Zhang M, Chen DY, Zhai ZH, Shu HB , RBCK1 negatively regulates TNF- and IL-1-triggered NF-κB activation by targeting TAB2/3 for degradation. , J Biol Chem. , 2007 , 282:16776-16782.
10. Zhang Y, Tian Y, Chen Q, Chen D, Zhai Z, Shu HB. , TTDN1 is a Plk1-interacting protein involved in maintenance of cell cycle integrity , Cell Mol Life Sci. , 2007 , 64:632-640.
11. Su X, Li S, Meng M, Qian W, Xie W, Chen D, Zhai Z, Shu HB , TRAF1 negatively regulates TRIF-mediated signaling. , European Journal of Immunology , 2006 , 36:199-206.
12. Zha J, Han K, Xu LG., Zhou Q, Chen D, Zhai Z, Shu HB. , The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IKK family members , Journal of Immunology , 2006 , 176:1072-1080
13. Huang J, Liu T, Chen D, Zhai Z, Shu HB , SIKE is an IKK-relative kinases-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways , EMBO Journal , 2005 , 24:4018-4028.
14. Huang J, Teng L, Li L, Liu T, Li L, Chen D, Xu LG, Zhai Z, Shu HB , ZNF216 is an A20-like and IKKγ -interacting inhibitor of NF-κB activation. , J Biol Chem. , 2005 , 279:16847-16853
15. Li L, Bin LH, Li F, Liu Y, Chen D, Zhai Z, Shu HB , TRIP6 is a RIP2-associated common signaling component of multiple NF-κB activation pathways , J Cell Sci. , 2005 , 118: 555-563
16. Zha J, Zhou Q, Xu LG, Chen D, Li L, Zhai Z, Shu HB , RIP5 is a RIP-homologous inducer of cell death , Biochem Biophys Res Commun. , 2004 , 319:298-303.
17. Chen D, Li Z, Yang Q, Zhang J, Zhai Z, Shu HB , Identification of a nuclear protein that promotes NF-κB activation. , Biochem Biophys Res Commun. , 2003 , 310:720-724
18. Chen D, Xu L, Chen L, Li L, Zhai ZH, Shu HB , NIK is a component of the EGF receptor signaling complexes , Oncogene , 2003 , 22:4348-4355
19. Huang J, Teng L, Liu T, Li L, Chen D, Li F, Xu LG, Zhai Z, Shu HB , Identification of a novel serine/threonine kinase that inhibits TNF-induced NF-κB activation and p53-induced transcription. , Biochem Biophys Res Commun. , 2003 , 309:774-778
20. Li Z, Zhang J, Chen D, Shu HB , Casper/c-FLIP is physically and functionally associated with NF-κB1 p105 , Biochem Biophys Res Commun. , 2003 , 309:980-985.
21. Chen D, Li X, Zhai Z, Shu HB , A novel zinc finger protein interacts with RIP and inhibits TNF-α and IL-1-induced NF-κB activation , J. Biol. Chem. , 2002 , 277:15985-15991. |
