异常的蛋白质泛素化与去泛素化修饰是肿瘤发生的重要原因。研究报道，许多病毒通过其编码的泛素化酶影响细胞内的信号通路，从而导致肿瘤发生与免疫抑制，但病毒编码的去泛素化酶及其作用机制还有待于深入研究。MDV是一种能引起禽类淋巴组织增生性肿瘤病（MD）的疱疹病毒，编码去泛素化酶UL36，但其通过UL36致瘤的机理还尚未阐明。本研究拟应用外源表达UL36的正常鸡淋巴细胞和沉默UL36的MD细胞，采用2D-MS等技术对比分析其蛋白质谱及泛素化修饰的变化，确定细胞内受UL36影响的信号通路；同时从MDV的致瘤蛋白Meq入手，分析在淋巴细胞内单独表达Meq以及与UL36共表达后细胞内Meq泛素化修饰的变化，以探讨UL36对Meq蛋白的去泛素化保护作用。通过本研究，不但确定UL36的细胞内调节通路及其在MDV致瘤中的作用，而且也为确切地阐明MD发生的分子机制提供理论依据。

The cellular protein ubiquitination is a dynamic and reversible modification which is catlyzed by ubiquitinase and deubiquitinase. The disorder of this process is one of the key reseans for tumorigenesis and immunosuppression. Many viral ubiquinases are able to induce cancer through disrupting the cellular ubiquin system, but little is known about viral deubiquitinases. Marek's disease (MD) is a T-cell lymphoma of chickens induced by Marek's disease virus (MDV). Deubiquitinase, UL36, but no ubiquitinase was found to be encoded by MDV. However, the function of UL36 in MD is still unknown. In the present proposal, 2D-DIGE and MS based proteome profiling is applied to identify the proteins and the signaling pathways affected by UL36 when it is expressed in T lymphocytes and knocked down in MDCC-MSB1 cells. Meanwhile, the alteration of Meq ubiquitination is analyzed in T lymphocytes expressing Meq or co-expressing with UL36 to illustrate the mechanism of Meq deubiquitination catalyzed by UL36. Our research would provide a comprehensive resource for the prevention and treatment of MD through determinating the function of UL36 and revealing the molecular mechanism of MD.