核糖体相关辅助伴侣分子-HSPA和MPP11调控树突状细胞分化发育的机制研究

树突状细胞(dendriticcell，DC)的正常分化是保证免疫应答和免疫自稳平衡的关键。细胞如何行之有效地组织特定转录因子、转录/表观调控因子调控细胞分化是当前的热点研究方向。“辅助伴侣”作用是组成核糖体相关复合物的异二聚体-HSPA14和MPP11的功能，MPP11还是一个新认定的、调控细胞分化的表观调控因子。然而，MPP11在 “辅助伴侣”和表观调控之间进行功能转换的机制不明。我们前期研究发现，HSPA14和MPP11在单核来源DC分化中具有等同的动态表达、负向调控作用，二者对MoDC的调控作用具有联动性。本课题拟从鉴定处于分化的MoDC 的HSP14和MPP11的修饰入手，探讨HSPA14对MPP11表达、修饰，胞浆/胞核转运和表观调控功能的影响。研究不仅发掘HSP14和MPP11的新作用，加深对DC分化的认识，还为细胞分化的转录调控机制以及髓系白血病致病机制拓展了新的研究基础。

The differentiation and development of dendritic cell (DC) are key to the balance between immune response and homeostasis. It is a leading study on the integrating mechanisms of transcriptional factors, transcription regulatory factors and epigenetic factors in the cellular differentiation and development. The heterodimer subunits-HSPA14 and MPP11 consist of ribosome-associated complex to play "cochaperon" roles, and MPP11 is a novel identified epigenetic regulatory factor in cellular differentiation. However, how to transform to transcriptional regulation from "cochaperon" by MPP11 is still unknown. We previously observed that the dynamic expression and effects on the differentiation of monocytes into DCs (MoDC) were similar between HSPA14 and MPP11, and that the role by HSPA14 is strongly linked to the role of MPP11 in the differentiation of MoDC. So, we will investigate what modified HSPA14 regulates the expression, modification, translocation from cytoplasma to nucleus and transcriptional regulation of MPP11 in the differentiation of MoDCs. The study not only explores the novel functions of HSPA14 and MPP11, and deepens the knowledge on the differentiation of DCs, but also provides the novel basis for the future study on the cellular differentiation and the development of myeloid leukemia.