鉴于本项目在发现酯酶D（ESD）调控细胞信号转导的新机制方面具有原创性，已作为应急项目获得了国家自然科学基金委的资助。最近我们新发现：１、ESD在细胞自噬调节和信号转导中发挥重要作用；２、一种新的小分子化合物能激活ESD、促进ESD与信号转导重要调控蛋白JAB1的相互作用，并提高JAB1的功能，3、在应急项目资助下，在ESD与JAB1互作的区域中又新鉴定出JAB1的T88、S94发生乙酰化；4、ESD还能参与调控p53的蛋白水平和活性。在此基础上，拟研究：1、ESD对JAB1的上述2个位点去乙酰化及其功能的调控作用；2、JAB1的S4、T88和S94去乙酰化与其磷酸化的关系；3、JAB1的乙酰化与其核定位分布的关系；4、ESD对JAB1的去乙酰化调控与p53的活性关系。为阐明ESD在细胞信号转导中的新作用机制提供实验证据。

This project is original in discovering a new mechanism for esterase D (ESD) regulation of cell signaling. It has been funded by the NSFC as an emergency project. Recently, we found that: 1, ESD played an important role in the regulation of autophagy and signal transduction; 2, A new small molecule could activate ESD,promote the interaction of ESD and JAB1 which is an important protein in signal transduction, and improve the function of JAB1; 3, Under the fundation of emergency project of NSFC, the amino acid sites (T88, S94) of JAB1 were newly identified that could be acetylated in the area of interaction between ESD and JAB1; 4, ESD also regulated the protein level and activity of p53. Based on these results, we will investigated: 1, the deacetylation regulation of ESD to JAB1 on the two sites mentioned above; 2, the relationship between JAB1 deacetylation of three amino acid residues sites (S4/T88 / S94) and phosphorylation; 3, the relationship between JAB1 acetylation and its nuclear localization distribution; 4, the relationship between JAB1 deacetylation and p53 activity. It would provide experimental evidence to elucidate the new mechanism of ESD in cell signal transduction.