Abstract
COP9 signalosome (CSN) and Den1/A deneddylases physically interact and promote multicellular development in fungi. CSN recognizes Skp1/cullin-1/Fbx E3 cullin-RING ligases (CRLs) without substrate and removes their posttranslational Nedd8 modification from the cullin scaffold. This results in CRL complex disassembly and allows Skp1 adaptor/Fbx receptor exchange for altered substrate specificity. We characterized the novel ubiquitin-specific protease UspA of the mold Aspergillus nidulans, which corresponds to CSN-associated human Usp15 and interacts with six CSN subunits. UspA reduces amounts of ubiquitinated proteins during fungal development, and the uspA gene expression is repressed by an intact CSN. UspA is localized in proximity to nuclei and recruits proteins related to nuclear transport and transcriptional processing, suggesting functions in nuclear entry control. UspA accelerates the formation of asexual conidiospores, sexual development, and supports the repression of secondary metabolite clusters as the derivative of benzaldehyde (dba) genes. UspA reduces protein levels of the fungal NF-kappa B-like velvet domain protein VeA, which coordinates differentiation and secondary metabolism. VeA stability depends on the Fbx23 receptor, which is required for light controlled development. Our data suggest that the interplay between CSN deneddylase, UspA deubiquitinase, and SCF-Fbx23 ensures accurate levels of VeA to support fungal development and an appropriate secondary metabolism.
Highlights
Mechanisms to defend against predators, pathogens, or harsh environmental conditions are well conserved among eukaryotes to increase chances of survival
The largest family is built by the ubiquitin-specific proteases (USPs) like in animals or yeast and includes CreB as only so far characterized deubiquitinating enzymes (DUBs) of
We investigated whether A. nidulans ubiquitin-specific protease A (UspA) interacts with the COP9 signalosome as it is described for the orthologous proteins in other organisms, including humans [19,20]
Summary
Mechanisms to defend against predators, pathogens, or harsh environmental conditions are well conserved among eukaryotes to increase chances of survival. A fast adaptive system inside cells is necessary to react to corresponding environmental stimuli. The ubiquitin-proteasome system (UPS) is the major pathway involved in proteome homeostasis in fungi and mammals that are evolutionarily separated already more than one billion years ago [1]. The covalent attachment and removal of posttranslational modifications alter properties of target proteins and enable a quick response to environmental stimuli without changing the whole transcriptional machinery in the cell. This can influence the activity of proteins, their binding to interaction partners, their subcellular localization, or their stability [2,3,4].
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