乳腺癌患者中Prohibitin（PHB）突变体的发现首次将PHB蛋白与人类的癌症联系在一起，随后的研究表明PHB是人类肿瘤抑制因子蛋白，能够通过E2F细胞周期调控途径影响细胞的增殖、分化、凋亡等，并被确定为癌症治疗的药物靶标蛋白。本项目将利用SPR、ChIP等方法分别在体外、体内研究PHB及其乳腺癌患者中发现的两种突变体与Rb蛋白之间的相互作用强度的变化，分析突变对于PHB功能的影响；并通过核磁共振波谱学的方法研究PHB与Rb蛋白相互作用的动态特性，分析二者发生相互作用的结构基础。在此基础上揭示PHB蛋白通过与Rb蛋白相互作用参与E2F细胞周期调控途径的分子机制，分析其功能的结构基础，为药物设计和开发提供线索。

Human prohibitin protein was first linked to human cancers by the discoveries of prohibitin mutations in breast cancers. Subsequent studies showed that PHB is a tumor suppressor involved in the E2F cell cycle regulation pathways that can affect cell proliferation, differentiation and apoptosis. And PHB has been identified as drug target protein for cancer treatment.The methods such as SPR, ChIP will be used in this project to find out the interaction strength changes between PHB, its mutants in breast cancer patients and Rb protein both in vitro and in vivo,and we will analyze the relationships between the mutations and the PHB functions.NMR spectroscopy methods will also be used to study the dynamic characteristics of the PHB and Rb protein interactions, and we will analyze the structural basis for the interactions.On these basis,it will be revealed the molecular mechanism of the protein interaction of PHB and Rb protein involved in the E2F-mediated cell cycle regulatory pathways, the structural basis for the PHB functions will be analyzed and the clues for drug design and development will be provided.