Interplay between controlled protein degradation, response to oxidative stress and polarized growth in Aspergillus fumigatus

在丝状真菌中，极化的真菌生长、氧化应激反应和控制蛋白质降解之间的相互作用尚未被探索。COP9信号体(CSN)位于这三个过程的交界处，控制着三种不同类型的基于cullin的多蛋白复合体的活性。CSN中的缺陷会导致超支化和对氧化应激的敏感性。在这个项目中，我们主要研究SCF(Skp1/cullin-1/F-box)E3泛素连接酶。SCF标记由26个蛋白酶体降解的蛋白质。其他SCF亚基是F-box蛋白，其功能是与泛素化的底物接合。我们将分析那些与极性和氧化损伤控制有关的F-box蛋白。我们将确定SCF底物，其降解是极化生长或/和适当的氧化应激反应所特别需要的，并且其存在会导致细胞故障。我们将确定氧化应激和极地生长过程中底物在细胞内的表达和位置。将检查相应基因的过度表达和缺失的表型。将与该联盟的其他合作伙伴合作，分析最有趣的F-box蛋白及其底物的基因同源，以确定它们在其他真菌的极性和氧化应激中的作用。

The interplay between polarized fungal growth, oxidative stress response and control of protein degradation is yet unexplored in filamentous fungi. The COP9 signalosome (CSN) is located at the interface of these three processes and controls the activity of three different types of cullin-based multiprotein complexes. Defects in CSN result in hyperbranching and sensitivity against oxidative stress. We focus in this project on the SCF (Skp1/cullin-1/F-box) E3 ubiquitin ligases. SCFs mark proteins for degradation by the 26 proteasome. Other SCF subunits are the F-box proteins, which function as adaptors for substrates that are ubiquitinated. We will analyse those F-box proteins, which are involved in polarity and oxidative damage control. We will identify the SCF substrates, whose degradation is specifically required for polarized growth or/and an appropriate oxidative stress response and whose presence results in cellular malfunction. We will determine the expression and location of the substrates within the cell during oxidative stress and polar growth. The phenotypes of overexpression as well as deletion of the corresponding genes will be examined. Homologs of the genes for the most interesting F-box proteins and their substrates will be analysed for their role in polarity and oxidative stress in other fungi in collaboration with the other partners in the consortium.