HDAC11是组蛋白去乙酰化酶(HDACs)家族Class IV的唯一成员，目前对其功能知之甚少。最近研究发现，HDAC11具有去ε-氨基长链脂肪酰化酶活性，但其下游底物和生物学功能尚不清楚。本项目拟针对HDAC11这一新的酶活性展开研究，并探索HDAC11在肿瘤中功能。我们前期工作筛选得到HDAC11特异性底物Galectin-1，据此提出HDAC11通过调节Galectin-1的酰化修饰和分子功能，影响肿瘤发生、发展及转移的过程。此外，将采用SILAC-LC-MS/MS联用的方法进一步筛选HDAC11的底物并探索修饰的功能。本项目拟采用特异性标记脂肪酰化修饰的方法验证HDAC11的底物，并应用一系列细胞生物学、分子生物学、肿瘤动物模型等方法验证科学假设。研究HDAC11分子机制及功能，对揭示蛋白ε-氨基长链脂肪酰化修饰的规律具有重要意义，为肿瘤等人类重大疾病的分子机制研究提供新思路。

Little is known about the function of HDAC11, which is the role member of Class IV histone deacetylase (HDACs). Recently it is reported that, HDAC11is an epsilon-N long chain fatty-acid deacylase, but its substrates and biological function remain unclear. Here, we will study around the new enzymatic activity of HDAC11, and its functions in tumor. Our previous studies indicated that fatty acylation of Galectin-1 is regulated by HDAC11. Based on the findings, we hypothesized that HDAC11 regulates development and metastasis in tumor via defatty-acylation of Galectin-1. Further, we will look for more special substrates of HDAC11 by SILAC-LC-MS/MS, and investigate the biological function of these modification. We will testify the substrates of HDAC11 with specially labeled fatty acylation and confirm the hypotheses by a series of methods including cell biological experiments, molecular biological experiments and mouse model. In summary, in-depth study the molecular mechanism and function of HDAC11, is of great significance on the illustration the rule of protein lysine fatty-acylation. Our study findings will help to provide new ideas for cancer and other major human diseases.