多发性骨髓瘤是由于血液中浆细胞恶化而形成的一种难治愈的血液癌症。尽管现在已有多种治疗方法使病人中位生存期有所提高，但是因其易复发和易产生耐药性等特征，这类疾病仍然无法治愈。因此发现新的致病机制和潜在的药物靶点将对该疾病的治疗有重要意义。我们的前期研究发现免疫调节药物来那度胺及其结构类似物结合蛋白cereblon (CRBN)能够和p53直接结合，并且调控着p53的核质分布。我们推测CRBN可能是通过影响p53核质分布来抑制多发性骨髓瘤细胞的增殖。为了证实这一假说，我们将进一步用蛋白表达、shRNA干扰、免疫沉淀、免疫印迹、免疫荧光、小鼠荷瘤等实验方法在细胞及动物模型中研究和证实CRBN和p53作用的结合位点，探明它们的相互作用对p53功能的调控和对多发性骨髓瘤细胞增殖的影响，为骨髓瘤的治疗提供潜在的药物靶点。

Multiple myeloma is one incurable blood cancer, which is characterized by the formation of malignant plasma cells in blood. Although the median survival of myeloma patients is improved in the recent years, this disease is still incurable due to its frequently relapse and resistance to currently available drugs. Therefore, it is useful for the treatment of multiple myeloma to investigate the pathogenesis and discover potential new therapeutic targets. Our preliminary results show that the immunomodulatory drug, such as lenalidomide and its structural analogs, binding protein cereblon (CRBN) directly interacts with p53, and regulates its nuclear-cytoplasmic distribution. Therefore, we propose that the regulation of CRBN on the nuclear-cytoplasmic distribution of p53 affects the proliferation of multiple myeloma cells. To prove this hypothesis, we will further identify the binding domain between CRBN and p53, explore the function of CRBN on p53, and the effect of CRBN-mediated p53 nuclear-cytoplamic distribution on the proliferation of multiple myeloma cells by performing protein expression, shRNA knockdown, immunoprecipitation, Western blotting, and immunocytochemistry in cell and animal models. We expect that our project will elucidate the molecular mechanism by which CRBN regulates the proliferation of myeloma cells and provide potential therapeutic targets for the disease treatment.