化疗耐药是急性髓系白血病（AML）患者死亡的主要原因。已知P-糖蛋白（P-gp）表达增高促进AML化疗耐药，但其调控机制仍不清楚。我们前期发现类泛素蛋白FAT10直接降解其底物蛋白进而促进肿瘤的发生发展。预实验发现：FAT10在耐药AML中高表达，降低FAT10的表达导致P-gp表达下降，且增加阿霉素的敏感性；通过质谱及免疫共沉淀发现虽然FAT10与P-gp不结合，但与其泛素E3连接酶FBXO15结合；进一步发现降低FAT10导致FBXO15增加，抑制泛素蛋白酶体降解可阻断FAT10对FBXO15的调控。据此，我们推测：FAT10直接降解FBXO15导致P-gp表达增加从而促进AML耐药。为证实这一假说，本研究拟从分子、细胞和整体水平，以免疫共沉淀和体外泛素化等方法，明确FAT10调控P-gp表达影响AML耐药的作用，再深入探讨FAT10调控P-gp的具体机制，为逆转AML耐药提供新思路。

Chemotherapy resistance is the main cause of death in patients with acute myeloid leukemia (AML). It has been known that increasing the expression of P-glycoprotein (P-gp) is associated with chemotherapy resistance while the its regulatory mechanism is still unclear. Our previous study had demonstrated that ubiquitin-like modifier FAT10 directly degraded its substrate proteins and further resulted in the development of tumors. In our previous research, FAT10 was highly expressed in AML patients with drug-resistant, and knockdown of FAT10 decreased the expression of P-gp and thus enhanced the sensitivity to adriamycin. The mass spectrometry and immunoprecipitation assays showed that FAT10 interacted with ubiquitin E3 ligase FBXO15, but not with P-gp. In addition, knockdown of FAT10 enhanced the expression of FBXO15, and inhibition of ubiquitin proteasome degradation blocked the regulatory effect of FAT10 on FBXO15. Therefore, we speculate that FAT10 influence the chemotherapy resistance in AML by increasing the P-gp expression via directly degrading FBXO15. To test this hypothesis, we performed this study at the cellular, molecular and overall levels, aiming to elucidate the action and mechanism of FAT10 regulation to P-gp expression on the chemotherapy resistance through immunoprecipitation and in vitro ubiquitination assays, and further explore the molecular mechanisms of P-gp regulation by FAT10, which would provide a novel option for reversing the drug resistance in AML.