MLL基因与ELL基因的移位融合形成的融合蛋白MLL-ELL是急性髓性白血病发生的重要原因，但对ELL的生物学功能知之甚少。近期，我们发现ELL是一类新的E3泛素连接酶，它能导致原癌蛋白c-Myc的泛素化降解，从而抑制肿瘤形成。此外，ELL的酶失活突变体ELL（C595A)不仅失去E3泛素连接酶活性，不能导致c-Myc降解，而且还能促进肿瘤转移。本研究旨在通过筛选和鉴定ELL的新靶标蛋白，分析ELL对新靶标蛋白的调控作用，弄清ELL是否通过对其靶标蛋白的调控来抑制肿瘤的形成和发展？诠释ELL（C595A)突变体促进肿瘤转移的分子机制，以期最终阐明ELL及其突变体在肿瘤形成、发展和转移过程中的作用和机制，为肿瘤的临床治疗和药物筛选奠定基础。

The fusion protein MLL-ELL resulted from translocation of MLL and ELL gene is the major cause of acute myeloid leukaemia (AML), but little is known about the function of ELL so far. Recently, we identified ELL as a novel E3 ligase, which can induce poly-ubiquitination and degradation of oncoproteion c-Myc to suppress tumor growth. In addition, ELL(C595A) mutant not only loses its E3 ligase activity and the ability for inducing c-Myc degradation, but also gains the ability to promote tumor metastasis. In this study, we propose to screen and identify novel targets of ELL and analyze the regulation of targets by ELL in order to understand whether the tumor suppression role of ELL is mediated by these targets. In addition, we propose to reveal the molecular mechanisms of ELL(C595A) in promoting metastasis. Eventually, we intend to demonstrate the role and mechanism of ELL and its mutant in tumor initiation, progression and metastasis, which will set up a basis for cancer treatment and drug screening.