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

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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.