Global analysis of the molecular roles, localizations and interactomes of F-box proteins during fungal development

Multiprotein complex, Skp-Cul-Fbox (SCF) E3 ubiquitin ligases, are the largest family of E3 ligases that are responsible for marking of target proteins with ubiquitin and subsequent proteasome-dependent degradation. SCF E3 ligases are involved in many cellular processes, including transcription, cell-cycle control by determining protein levels of target proteins. The F-box component of the SCF complex is essential for the substrate specificity of the SCF complex by recruiting target proteins for ubiuitination. In this study, we have systematically investigated the molecular functions of 73 F-box or F-box-like protein encoding genes of the eukaryotic model system Aspergillus nidulans. Deletion of 73 fbx genes revealed that only 8-10 % of the fbx genes are required for proper fungal development and light response. Only fbx25, which encodes SconB necessary for sulphur metabolism, is essential for fungal growth and survival. 50 % of the F-box proteins (30-35) are associated with the SCF complexes through the adaptor SkpA protein during fungal development. Several F-box proteins show development and stress specific interactions with the SkpA protein. 30 % of the F-box proteins are exclusively localized to the nuclear fraction whereas the rest show other localization patterns including, cytoplasmic, hyphal tip and plasma membrane. High scoring F-box proteins (Fbx1 to Fbx48) interact with more than 1500 proteins including SkpA and CullinA. These data suggest that F-box proteins interact with at least 15% of the total proteome and control developmental responses to environmental stimuli and stresses.