泛素化是一种重要的翻译后修饰方式,这种修饰参与真核细胞的多种途径以及环境胁迫应答.与传统的K48连接多聚泛素化介导蛋白降解的方式不同,K63连接多聚泛素化参与调控蛋白质活性,而这一过程需要Ubc13-Uev异源二聚体作为E2.多数多细胞生物中含有一个UBC13但却有多个UEV基因,暗示着Uev在上述过程中充当调节亚基.我们实验室首先报道了酵母、哺乳动物和植物细胞中的UBC13和Uev基因.我们最近发现一些植物的UEV基因含有一个C端异戊烯修饰基序,这一基序通常参与蛋白质膜锚定或者调节蛋白间相互作用.本项目中,我们将就Uev蛋白异戊烯化如何参与调节Ubc13-Uev活性进行研究,并寻找相应的E3以及底物.因为我们最近发现植物Ubc13缺失会展现出多种发育以及胁迫应答缺陷,我们期待这一项目可以解答泛素化和异戊烯化两种不同的蛋白修饰方式是如何相互作用并参与到诸如激素信号及自然免疫等植物生理过程.

Ubiquitination is a means of post-translational modification that plays an important role in eukaryotic cellular processes and response to environmental stresses. Differing from the conventional K48-linked polyubiquitination that targets protein for degradation, K63-linked polyubiquitination is believed to alter the target protein activity, and this process requires a Ubc13-Uev heterodimer as a E2. Most multicellular eukaryotic organisms contain one UBC13 gene but multiple UEV genes, suggesting that Uev is a regulatory subunit of the above process. My laboratory reported initial isolation and functional characterization of UBC13-UEV genes from yeast and mammalian cells, and recently reported the similar studies in plants. More recently, we found that a subgroup UEV genes from plants contain a consensus C-terminal motif indicative of lipid modifications known as prenylation, which often makes modified proteins membrane-bound or alters protein-protein interaction. In this project, we will investigate how plant Uev protein prenylation is involved in the regulation of the Ubc13-Uev activity, and to search for their cognate E3s and substrates. Since we recently found that plants lacking Ubc13 display multiple developmental and stress response defects, we anticipate that this proposed study will help us to understand how two protein modifications interplay in the regulation of important plant bioprocesses such as hormone signaling and innate immunity.