Integration of the catalytic subunit activates deneddylase activity <i>in vivo</i> as final step in fungal <scp>COP</scp>9 signalosome assembly

Beckmann, Elena A.; Köhler, Anna M.; Meister, Cindy; Christmann, Martin; Draht, Oliver; Rakebrandt, Nikolas; Valerius, Oliver; Braus, Gerhard H.

doi:10.1111/mmi.13017

Cited by 21 publications

(70 citation statements)

References 54 publications

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“…However, consistent with our model of eIF3 assembly, N. crassa KOs of Csn4 or 6 (paralogs of eIF3a or f) are lethal, suggesting they assemble prior to dispensable subunits Csn1, 2, 3, and 5 (paralogs of eIF3e, c, l, and h) (Colot et al, 2006). However, one notable difference is that Csn5 (eIF3h paralog) is thought to be the final subunit to be incorporated (Beckmann et al, 2015; Enchev et al, 2012), affecting the activity of the CSN, but not its structure (Zhou et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion

et al. 2016

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SUMMARY Eukaryotic initiation factor 3 (eIF3), an essential multi-protein complex involved in translation initiation, is composed of 12 tightly associated subunits in humans. While the overall structure of eIF3 is known, the mechanism of its assembly and structural consequences of dysregulation of eIF3 subunit expression seen in many cancers is largely unknown. Here we show that subunits in eIF3 assemble into eIF3 in an interdependent manner. Assembly of eIF3 is governed primarily by formation of a helical bundle, composed of helices extending C-terminally from PCI-MPN domains in eight subunits. We propose that, while the minimal subcomplex of human-like eIF3 functional for translation initiation in cells consists of subunits a, b, c, f, g, i, and m, numerous other eIF3 subcomplexes exist under circumstances of subunit over- or underexpression. Thus, eIF3 subcomplexes formed or “released” due to dysregulated subunit expression may be determining factors contributing to eIF3-related cancers.

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Section: Discussionmentioning

confidence: 99%

Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion

et al. 2016

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“…The multiprotein complex COP9 signalosome represents a deneddylase, which removes Nedd8 and is involved in the coordination of sexual development and secondary metabolism. The defects in genes for COP9 subunits are genetically epistatic to mutations in genes for velvet domain proteins in A. nidulans (382)(383)(384), but the exact molecular mechanism of velvet domain protein stability control is as yet unknown (385,386). DenA represents a second deneddylase, which interacts at septa with the DenA-interacting protein DipA.…”

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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288

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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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“…The only intrinsic enzymatic function of the CSN complex is represented by its MPN isopeptidase activity against cullins modified with Nedd8 [ 22 , 23 ]. Its deneddylase activity is harbored within CSN5 which is the last subunit that is integrated into a seven subunit pre-complex [ 24 , 25 ]. All eight CSN subunits are required for the holocomplex acting as denedddylase.…”

Section: Introductionmentioning

confidence: 99%

The DenA/DEN1 Interacting Phosphatase DipA Controls Septa Positioning and Phosphorylation-Dependent Stability of Cytoplasmatic DenA/DEN1 during Fungal Development

et al. 2016

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DenA/DEN1 and the COP9 signalosome (CSN) represent two deneddylases which remove the ubiquitin-like Nedd8 from modified target proteins and are required for distinct fungal developmental programmes. The cellular DenA/DEN1 population is divided into a nuclear and a cytoplasmatic subpopulation which is especially enriched at septa. DenA/DEN1 stability control mechanisms are different for the two cellular subpopulations and depend on different physical interacting proteins and the C-terminal DenA/DEN1 phosphorylation pattern. Nuclear DenA/DEN1 is destabilized during fungal development by five of the eight CSN subunits which target nuclear DenA/DEN1 for degradation. DenA/DEN1 becomes stabilized as a phosphoprotein at S243/S245 during vegetative growth, which is necessary to support further asexual development. After the initial phase of development, the newly identified cytoplasmatic DenA/DEN1 interacting phosphatase DipA and an additional developmental specific C-terminal phosphorylation site at serine S253 destabilize DenA/DEN1. Outside of the nucleus, DipA is co-transported with DenA/DEN1 in the cytoplasm between septa and nuclei. Deletion of dipA resulted in increased DenA/DEN1 stability in a strain which is unresponsive to illumination. The mutant strain is dysregulated in cytokinesis and impaired in asexual development. Our results suggest a dual phosphorylation-dependent DenA/DEN1 stability control with stabilizing and destabilizing modifications and physical interaction partner proteins which function as control points in the nucleus and the cytoplasm.

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Integration of the catalytic subunit activates deneddylase activity in vivo as final step in fungal COP9 signalosome assembly

Cited by 21 publications

References 54 publications

Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion

Assembly of eIF3 Mediated by Mutually Dependent Subunit Insertion

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

The DenA/DEN1 Interacting Phosphatase DipA Controls Septa Positioning and Phosphorylation-Dependent Stability of Cytoplasmatic DenA/DEN1 during Fungal Development

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