SUMO介导的泛素连接酶RNF4在斑马鱼胚胎造血发育中的生物学意义研究

环指蛋白4（ring finger protein 4, RNF4）作为脊椎动物中一类特殊的类泛素化介导的泛素连接酶(sumo-targeted ubiquitin ligase,STUbL)特异性地参与类泛素化（SUMO）修饰底物蛋白的降解调控。蛋白质修饰及降解的失调与癌症和神经退变性疾病这两类重大疾病密切相关。参与造血调控的多种关键转录因子均可被SUMO化修饰，因此本课题将首次以斑马鱼为研究模型，利用MO反义寡核苷酸链介导的基因knockdown技术和TALEN介导的基因knockout技术以及分子生物学，生物化学，细胞生物学和发育生物学等多种实验方法来研究RNF4是如何通过调控相关关键转录因子，从而影响造血发育分化过程。这将有助于在分子机制方面深入理解蛋白质翻译后修饰以及降解的调控在造血精细发育过程中的生物学作用。

The SUMO-targeted ubiquitin ligases (STUbLs) RNF4 is involved in the regulation of its sumoylated targets degradation. Dysregulation of protein modification and degradation is tightly related with cancer and degenerative diseases. A series of key transcription factors implicated in hematopoiesis could be sumoylated, so in this study we'll use MO mediated gene knockdown and TALEN mediated gene knockout technology as well as a variety of experimental methods to reveal how RNF4 acts in hematopoiesis by regulating key transcription factors. This will help us to understand more deeply of the functional role of post-translational modification and degradation in the well-tuned hematopoiesis regulation.