自噬与肿瘤密切相关，但其与肿瘤分化的关系存在争论、机制尚不明确。神经母细胞瘤是自行分化率最高的肿瘤之一，我们选其作为研究模型。前期研究发现CaMKII能上调Beclin1 S90磷酸化水平，导致Bcl-2与之结合下降。进一步研究显示分化抑制蛋白Id1也可能被CaMKII磷酸化，促进其K63位泛素化修饰，并与自噬受体p62结合。基于此，我们提出“CaMKII激活自噬介导Id1蛋白降解促进神经母细胞瘤分化”的科学假说，拟利用质谱分析、免疫共沉淀及激酶反应等技术，获得CaMKII磷酸化Beclin 1的证据，探讨其对自噬的影响；寻找CaMKII磷酸化Id1的证据，证实Id1经自噬途径降解的过程；并利用神经母细胞瘤细胞系、动物成瘤模型及临床病人样本，观察该过程促进神经母细胞瘤分化的作用。本项目以自噬和分化作为切入点深入研究，探讨其分子机制，有望为神经母细胞瘤的治疗提供更有效的思路和方法。

Emerging studies have suggested autophagy is closely related to tumor, however, the mechanisms underlying the role of autophagy in tumor differentiation remains unclear. Human neuroblastoma is known for its high level of self-differentiation. Our preliminary studies show that the activation of CaMKII kinase increased the phosphorylation of Beclin1 S90, which resulted in the dissociation of Bcl-2/Beclin 1 complex. Further studies have shown that activation of CaMKII also induced the phosphorylation of inhibitor of differentiation-1 (Id1), leading to the ubiquitination of Id1 at K63, which was further subjected for degradation via selectively binding to P62. Based on these results, we hypothesize that CaMKII induces autophagic degradation of Id1 and promotes cell differentiation in neuroblastoma cells. And we will use bioinformatics, immunoprecipitation and in vitro kinase assay, to demonstrate that CaMKII can induces autophagy via Beclin phosphorylation and further induce autophagic degradation of Id1, which is essential in promoting the differentiation of neuroblastoma. This study will gain new insights for the function of autophagy, and also shed the light on the development of future neuroblastoma therapy.