肿瘤耐药是造成肿瘤化疗失败的主要原因之一。因此，研究肿瘤耐药的机制并逆转耐药具有重要意义。很多研究对肿瘤耐药的分子机制进行了阐述，其中自噬和凋亡在肿瘤治疗和耐药中的作用近年来收到广泛关注。申请人已发表的工作对凋亡和自噬相关家族蛋白在肿瘤治疗中的作用进行了研究，进一步的研究首次发现在肿瘤治疗中，Naa10p/ARD1通过调控Atg5的乙酰化修饰，从而可能在肿瘤治疗过程中调控肿瘤细胞的死亡和自噬。这些结果显示在肿瘤发生，发展和治疗过程中，可能Naa10p/ARD1-Atg5新通路能作为介导自噬和凋亡转换的开关。本项目在此基础上运用蛋白组学，GST pull-down，免疫沉淀等技术研究Naa10p/ARD1和Atg5的相互作用，以及这个新通路在自噬，凋亡和肿瘤发生中的功能及分子机制，揭示其在肿瘤治疗中调控凋亡和自噬的作用。

Chemoresistance is a major obstacle to successful cancer therapy. Although previous studies have described some molecular mechanisms of chemoresistance, the function of autophagy or apoptosis in chemoresistance and tumor therapy still need to be studied. Our previous printed reports revealed some autophagy and apoptosis-dependent proteins played an important role in tumor therapy. Now, our study revealed that Naa10p/ARD1 acetylated Atg5 to regulate autophagy and apoptosis. These results indicate that Naa10p/ARD1-Atg5 pathway could regulate autophagy and apoptosis as the axis in cancer therapy. So we speculate that Naa10p/ARD1 mediated-Atg5 signaling pathway modulates autophagy and apoptosis in cancer therapy. We will use a variety of techniques (proteomics, GST pull-down assay, immunoprecipitation, etc) to study the function interaction of Naa10p/ARD1 with Atg5. We hope to find the molecular networks of Naa10p/ARD1-Atg5 pathway and demonstrate the function of Naa10p/ARD1-Atg5 signaling pathway in autophagy and cancer therapy. We will elucidate the molecular mechanism of Naa10p/ARD1-Atg5 pathway in tumorigenesis and advanced malignancy. These findings will provide new theoretical basis for cancer therapy.