Recent Progress of Deubiquitinating Enzymes in Human and Plant Pathogenic Fungi

Abstract

In eukaryotic cells, a large number of proteins are modified by ubiquitination, which leads to proteasomal degradation or change in protein function. The protein ubiquitination process can be reversed by a process called deubiquitination, which plays an important regulatory mechanism in cellular control. Deubiquitination is catalyzed by deubiquitinating enzymes (DUBs); the cysteine proteases specifically cleave off ubiquitin from ubiquitinated substrates or ubiquitin precursors. Over the past two decades, components of different DUB families have been found to play important roles in both human and plant pathogenic fungi. Given the importance of DUBs for fungal development and virulence, in this review, we concentrate on recent findings and new insights into the roles of DUBs in different fungal pathogens, with a focus on infection-related morphogenesis and virulence, as well as their roles in development and stress response. We also summarize the DUBs-mediated regulatory mechanisms during the above processes. These findings should allow us to develop novel inhibitors to control fungal pathogens.

Degradation of α-Subunits, Doa1 and Doa4, are Critical for Growth, Development, Programmed Cell Death Events, Stress Responses, and Pathogenicity in the Watermelon Fusarium Wilt Fungus Fusarium oxysporum f. sp. niveum

“…48 In addition to WD40 domain, Doa1 contains PFU and PUL domains, 25 whereas Doa4 consists of DUSP and UCH domains. 29 However, the precise role of each domain in phytopathogenic fungi remains unclear. Our results demonstrate that all conserved domains of FonDoa1 are essential for its function in the Fon infection process, as different domains of Doa1 could not independently restore the pathogenicity defect (Figure 5).…”

“…The WD-repeat domain of Doa1 has been shown to regulate diverse cellular functions, such as regulation of signal transduction, transcription, pre-mRNA processing, or cell structure maintenance . In addition to WD40 domain, Doa1 contains PFU and PUL domains, whereas Doa4 consists of DUSP and UCH domains . However, the precise role of each domain in phytopathogenic fungi remains unclear.…”

“…cerevisiae. , Doa1 and its orthologues contain N-terminal ubiquitin-binding domains, WD40 and PFU, and a C-terminal Cdc48-interacting domain, PUL . Conversely, Doa4 belongs to a highly conserved protease superfamily containing two different catalytic domains, an N-terminal domain present in ubiquitin-specific protease (DUSP) and an ubiquitin-specific protease C-terminal hydrolase (UCH) . Besides maintaining ubiquitin homeostasis, Doa1 or Doa4 and other related proteins also govern the turnover of the ubiquitinated substrates by preventing their proteolysis.…”

“…25 Conversely, Doa4 belongs to a highly conserved protease superfamily containing two different catalytic domains, an N-terminal domain present in ubiquitin-specific protease (DUSP) and an ubiquitin-specific protease C-terminal hydrolase (UCH). 29 Besides maintaining ubiquitin homeostasis, Doa1 or Doa4 and other related proteins also govern the turnover of the ubiquitinated substrates by preventing their proteolysis. For example, Lub1 was reported to govern ubiquitin homeostasis and stress responses in S. pombe by maintaining the cellular ubiquitin level.…”

Profiling of deubiquitinases that control virulence in the pathogenic plant fungus Fusarium graminearum

“…A previous study demonstrated that in Saccharomyces cerevisiae , Dubs are crucial for various biological processes such as stress response, pre‐mRNA editing, protein sorting, and transport (Hutchins et al ., 2013). Beyond yeast, the role of deubiquitinating enzymes in pathogenic fungi has also been documented (Wang et al ., 2022). For instance, the deubiquitinating enzyme Ubp3 influences appressorium formation and maturation by targeting the GTPase‐activating protein Smo1 for deubiquitination in Magnaporthe oryzae (Cai et al ., 2022).…”