Nucleophosmin蛋白修饰变化在肿瘤细胞增殖分化与凋亡调控中的作用机制研究

我们的研究证实Nucleophosmin（NPM）是不同肿瘤细胞增殖、分化与凋亡的共同差异核基质蛋白，确证NPM与 c-Fos、c-Myc、P53和Rb相互作用及它们在肿瘤细胞分化与凋亡过程中存在共定位和移位改变，NPM是肿瘤细胞增殖分化与凋亡调控关键作用节点和重要功能调控蛋白，在肿瘤细胞分化过程中NPM 蛋白磷酸化水平下降。为此，我们拟进一步检测NPM及其相互作用蛋白的修饰类型和修饰程度变化，比较不同的细胞分化和凋亡诱导物对NPM蛋白修饰变化影响和全细胞与核基质蛋白中NPM蛋白修饰差异，筛查NPM相互作用蛋白、观察NPM与其相互作用蛋白的亚细胞定位与转运变化。阐明NPM蛋白修饰变化在肿瘤细胞增殖分化与凋亡调控中的作用机制，以此为切入点整合肿瘤细胞增殖分化与凋亡的分子调控网络。找出细胞增殖、分化与凋亡调控机理研究新方向，为以NPM为靶向性蛋白的病理诊断和药物研究提供充分科学依据。

Our research has confirmed that nucleophosmin (NPM) is a commom differential nuclear matrix protein in the proliferation, differentiation and apoptosis of different tumor cells. In addition, it has confirmed the interaction between NPM and c-Myc,c-Fos,P53 and Rb, and their alteration of co-localization and movement during the differentiation and apoptosis of tumor cells. NPM is a key point of the regulation and an important functional regulated protein in the proliferation, differentiation and apoptosis of carcinoma cells. The phosphorylation level of NPM descended during the differentiation of tumor cells. Based on the above-mentioned works, we plan to investigate the different types and degrees of modification of NPM and its interactional proteins, to compare the different influences of cell differentiation and nuclear apoptosis inducer on the protein modification, to screen and examine the proteins' interact with NPM, and to observe the ultrastructure localization and alteration of NPM and its interaction proteins. The present research will clarify the mechanism of the alteration of NPM modification during the proliferation, differentiation and apoptosis of tumor cells, and integrate the molecular regulating network of the proliferation, differentiation and apoptosis of tumor cells. These results will be able to provide a new direction for the studies on regulative mechanism of cellular proliferation, differentiation and apoptosis, and offer sufficient scientific foundation to pathological diagnosis and pharmaceutic research targeting on NPM.