m6A修饰的甲基转移酶复合物METTL3/METTL14在个体的生长发育，以及肿瘤的发生发展中发挥着重要作用，但目前对METTL3/METTL14复合物活性调节的研究相对欠缺。METTL14第399位丝氨酸存在着高可信度的磷酸化修饰，且该位点磷酸化水平在Basal类型的乳腺癌中显著下调，但该磷酸化位点的功能及调控机制尚不清楚。我们提出以下假设：S399位点的磷酸化通过影响METTL14蛋白功能从而影响Basal类型乳腺癌的发生与发展。本研究将从蛋白翻译后修饰的角度，研究METTL14的S399磷酸化修饰参与乳腺癌发生发展的机制。我们将利用S399突变体研究其磷酸化对METTL14蛋白生化特性及功能的影响，通过筛选并鉴定特异激酶以研究其磷酸化水平的动态变化，通过突变体及激酶抑制剂观察S399磷酸化对不同类型乳腺癌发生发展的影响从而为该类型乳腺癌的治疗提供新思路。

m6A methyltransferase complex METTL3/METTL14 plays an important role in development and tumorigenesis, but an understanding of how METTL3/METTL14 regulated is still very limited. Phosphorylation of S399 on METTL14 has been detected in many proteome works, and is significantly low in Basal type breast cancer. We hypothesis phosphorylation of S399 affect METTL14 function and thus impact the tumorigenesis of Basal breast cancer. We plan to understand the mechanism of METTL14 phosphorylation in regulating breast cancer. We plan to observe the biochemical and biological differences between wildtype METTL14 and its S399 mutants; to screen the specific kinase of S399 phosphorylation and observe its dynamic change; to use S399 mutants and kinase inhibitors to test S399 phosphorylation on Basal breast cancer development. This study might shed light on treating Basal type breast cancer.