SCF Ubiquitin Ligase F-box Protein Fbx15 Controls Nuclear Co-repressor Localization, Stress Response and Virulence of the Human Pathogen Aspergillus fumigatus

Jöhnk, Bastian; Bayram, Özgür; Abelmann, Anja; Heinekamp, Thorsten; Mattern, Derek J.; Brakhage, Axel A.; Jacobsen, Ilse D.; Valerius, Oliver; Braus, Gerhard H.

doi:10.1371/journal.ppat.1005899

Cited by 41 publications

(45 citation statements)

References 78 publications

(131 reference statements)

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“…The CSN complex plays a key role in the oxidative stress response. The CSN complex might physically interact with Fbx15, which is required for oxidative stress tolerance and development in Aspergillus (von Zeska Kress et al, 2012;Joehnk et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In S. cerevisiae, Rfx1 forms a complex with transcriptional corepressors Ssn6/Cyc8 and Tup1, which directly interacts with Sfl1 to suppress FLO11 expression for flocculation (Conlan & Tzamarias, 2001;Ansanay Galeote et al, 2007). Aspergillus fumigatus AfSsnF corresponding to yeast Ssn6 is required for stress response and pathogenicity (Joehnk et al, 2016). Rfx1 of the plant pathogenic fungus Fusarium graminearum plays critical roles in DNA damage repair, conidiation, fungal growth, and pathogenicity (Huang et al, 1998;Min et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Verticillium dahliae transcription factors Som1 and Vta3 control microsclerotia formation and sequential steps of plant root penetration and colonisation to induce disease

et al. 2018

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Summary Verticillium dahliae nuclear transcription factors Som1 and Vta3 can rescue adhesion in a FLO8‐deficient Saccharomyces cerevisiae strain. Som1 and Vta3 induce the expression of the yeast FLO1 and FLO11 genes encoding adhesins. Som1 and Vta3 are sequentially required for root penetration and colonisation of the plant host by V. dahliae. The SOM1 and VTA3 genes were deleted and their functions in fungus‐induced plant pathogenesis were studied using genetic, cell biology, proteomic and plant pathogenicity experiments. Som1 supports fungal adhesion and root penetration and is required earlier than Vta3 in the colonisation of plant root surfaces and tomato plant infection. Som1 controls septa positioning and the size of vacuoles, and subsequently hyphal development including aerial hyphae formation and normal hyphal branching. Som1 and Vta3 control conidiation, microsclerotia formation, and antagonise in oxidative stress responses. The molecular function of Som1 is conserved between the plant pathogen V. dahliae and the opportunistic human pathogen Aspergillus fumigatus. Som1 controls genes for initial steps of plant root penetration, adhesion, oxidative stress response and VTA3 expression to allow subsequent root colonisation. Both Som1 and Vta3 regulate developmental genetic networks required for conidiation, microsclerotia formation and pathogenicity of V. dahliae.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Verticillium dahliae transcription factors Som1 and Vta3 control microsclerotia formation and sequential steps of plant root penetration and colonisation to induce disease

et al. 2018

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“…This protein controls septum positioning and asexual spore formation (387). F-box proteins involved in fungal development include GrrA, which is required during late fruiting body formation for ascospore maturation (388), or Fbx15, which is required for asexual and sexual development in A. nidulans (389) or for virulence in A. fumigatus (390).…”

Section: Fruiting Body Formationmentioning

confidence: 99%

Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction and Infection Structures

Riquelme

Aguirre

Bartnicki-García

et al. 2018

Microbiol Mol Biol Rev

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SUMMARYFilamentous fungi constitute a large group of eukaryotic microorganisms that grow by forming simple tube-like hyphae that are capable of differentiating into more-complex morphological structures and distinct cell types. Hyphae form filamentous networks by extending at their tips while branching in subapical regions. Rapid tip elongation requires massive membrane insertion and extension of the rigid chitin-containing cell wall. This process is sustained by a continuous flow of secretory vesicles that depends on the coordinated action of the microtubule and actin cytoskeletons and the corresponding motors and associated proteins. Vesicles transport cell wall-synthesizing enzymes and accumulate in a special structure, the Spitzenkörper, before traveling further and fusing with the tip membrane. The place of vesicle fusion and growth direction are enabled and defined by the position of the Spitzenkörper, the so-called cell end markers, and other proteins involved in the exocytic process. Also important for tip extension is membrane recycling by endocytosis via early endosomes, which function as multipurpose transport vehicles for mRNA, septins, ribosomes, and peroxisomes. Cell integrity, hyphal branching, and morphogenesis are all processes that are largely dependent on vesicle and cytoskeleton dynamics. When hyphae differentiate structures for asexual or sexual reproduction or to mediate interspecies interactions, the hyphal basic cellular machinery may be reprogrammed through the synthesis of new proteins and/or the modification of protein activity. Although some transcriptional networks involved in such reprogramming of hyphae are well studied in several model filamentous fungi, clear connections between these networks and known determinants of hyphal morphogenesis are yet to be established.

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“…In A. fumigatus, AfFbx15 with two putative NLS sites mainly accumulates in the nucleus in response to oxidative stress. In addition, AfFbx15 can regulate the transcriptional repressor Ssn6 in an SCF-independent manner (Johnk et al, 2016). Comparably, MoFbx15 was also mobilized to the nucleus and highly expressed in invasive hyphae, suggesting a role in colonization and expansion in host cells.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, MoFbx15 may function without forming an SCF complex. On the other hand, A. fumigatus Fbx15, a homologue of MoFbx15, was confirmed to interact with Skp1 using a bimolecular fluorescence complementation approach (Johnk et al, 2016). Thus, complementary approaches may be needed to determine the underlying molecular mechanisms.…”

Section: Discussionmentioning

confidence: 99%

F‐box proteins MoFwd1, MoCdc4 and MoFbx15 regulate development and pathogenicity in the rice blast fungus Magnaporthe oryzae

Shi

Chen

Zhu

et al. 2019

Environmental Microbiology

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Summary The Skp1‐Cul1‐F‐box‐protein (SCF) ubiquitin ligases are important parts of the ubiquitin system controlling many cellular biological processes in eukaryotes. However, the roles of SCF ubiquitin ligases remain unclear in phytopathogenic Magnaporthe oryzae. Here, we cloned 24 F‐box proteins and confirmed that 17 proteins could interact with MoSkp1, showing their potential to participate in SCF complexes. To determine their functions, null mutants of 21 F‐box‐containing genes were created. Among them, the F‐box proteins MoFwd1, MoCdc4 and MoFbx15 were found to be required for growth, development and full virulence. Fluorescent‐microscopy observations demonstrated that both MoFbx15 and MoCdc4 were localized to the nucleus, compared with MoFwd1, which was distributed in the cytosol. MoCdc4 and MoFwd1 bound to MoSkp1 via the F‐box domain, the deletion of which abrogated their function. Race tube and qRT‐PCR assays confirmed that MoFwd1 was involved in circadian rhythm by regulating transcription and protein stability of the core circadian clock regulator MoFRQ. Moreover, MoFWD1 also orchestrates conidial germination by influencing conidial amino acids pools and oxidative stress release. Overall, our results indicate that SCF ubiquitin ligases play indispensable roles in development and pathogenicity in M. oryzae.

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SCF Ubiquitin Ligase F-box Protein Fbx15 Controls Nuclear Co-repressor Localization, Stress Response and Virulence of the Human Pathogen Aspergillus fumigatus

Cited by 41 publications

References 78 publications

Verticillium dahliae transcription factors Som1 and Vta3 control microsclerotia formation and sequential steps of plant root penetration and colonisation to induce disease

Verticillium dahliae transcription factors Som1 and Vta3 control microsclerotia formation and sequential steps of plant root penetration and colonisation to induce disease

Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction and Infection Structures

F‐box proteins MoFwd1, MoCdc4 and MoFbx15 regulate development and pathogenicity in the rice blast fungus Magnaporthe oryzae

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