目前在我国各地区肿瘤中，白血病的发病率占第六位。白血病的发病与造血干细胞（HSC）稳态密切相关。泛素化-E3连接酶在造血系统中起着重要的作用，E3连接酶的缺失会影响HSC的静息期，进而导致造血干细胞的扩增。例如E3连接酶c-cbl的敲除引起造血干细胞自我更新增强、异常的干细胞增殖，最终导致骨髓增生性疾病和急性髓系白血病。E3连接酶TRIM31在细胞内信号传导、先天免疫、转录、自噬和致癌等细胞过程中起关键作用。本项目的前期数据显示，TRIM31作为CDK8的泛素化E3连接酶，调控其泛素化与降解。而CDK8是一个已知肿瘤因子，与白血病密切相关，抑制CDK8的酶活性可以有效地抑制白血病。本项目是利用TRIM31基因敲除小鼠，研究其通过调节CDK8的泛素化，从而影响造血干细胞稳态，功能及白血病发生过程。研究目的在于：通过调节TRIM31的表达而达到治疗白血病和抗衰老。

At present, the incidence of leukemia is the sixth highest among tumors in all regions of China. The pathogenesis of leukemia is closely related to the homeostasis of hematopoietic stem cells (HSC). Ubiquitin-E3 ligase plays an important role in the hematopoietic system. The absence of E3 ligase can affect the resting period of HSC and lead to the proliferation of hematopoietic stem cells. For example, the knockout of E3 ligase c-Cbl leads to the enhancement of hematopoietic stem cell self-renewal and abnormal stem cell proliferation, which eventually leads to myeloproliferative diseases and acute myeloid leukemia. E3 ligase TRIM31 plays a key role in cell signaling, innate immunity, transcription, autophagy and carcinogenesis. Previous data of this project show that TRIM31, as an ubiquitinated E3 ligase of CDK8, regulates its ubiquitination and degradation. CDK8 is a known tumor factor, which is closely related to leukemia. Inhibiting the activity of CDK8 can effectively inhibit leukemia. This project is to study the effects of TRIM31 gene knockout mice on the homeostasis, function and leukemia process of hematopoietic stem cells by regulating the ubiquitination of CDK8. The aim of this study is to treat leukemia and anti-aging by regulating the expression of TRIM31.