锌指转录因子Miz1在细胞周期、程序性细胞死亡（细胞凋亡）及炎症反应中起到重要的作用。我们前期的工作证明细胞质中的Miz1以不依赖于它转录活性的形式干涉JNK1活化，从而抑制肿瘤坏死因子（TNF）诱导的细胞凋亡和炎症反应。另一方面，我们还证明细胞核中的Miz1 能够通过抑制C/EBPδ的表达来抑制肿瘤坏死因子诱导的炎症反应。最近我们的研究发现：在淋巴毒素(LT)刺激下，细胞质Miz1 能够调节非经典的NF-κB通路。在本项目中我们计划研究：Miz1调节非经典NF-κB通路的分子机制，淋巴发育信号对Miz1的调节，以及Miz1在二级淋巴器官发育中的作用。这项研究将为开发更有选择性的、更有效的疾病治疗方法提供分子基础。

The zinc finger transcription factor Miz1 plays a critical role in cell cycle progression, programmed cell death (apoptosis) and inflammation through transcriptional and post-translational regulation. Previously, we uncovered that the cytoplasmic Miz1 can suppress tumor necrosis factor (TNF)-induced apoptosis and inflammatory responses through interfering with JNK1 activation independently of its transcriptional activity, while the nuclear Miz1 can repress TNF-induced inflammatory responses through inhibition of C/EBP expression. Recently, we found that the cytoplasmic Miz1 is able to regulate non-canonical NF-κB pathway in response to lymphotoxin β (LTβ). In this proposal, we plan to investigate the molecular mechanisms by which Miz1 regulates the non-canonical NF-κB pathway, the regulation of Miz1 by developmental cues and the role of Miz1 in the development of secondary lymphoid organs. The successful completion of this study should provide a molecular basis for developing more selective and efficient new therapeutics for the treatment of human diseases.