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    Regulation of Aspergillus nidulans CreA-Mediated Catabolite Repression by the F-Box Proteins Fbx23 and Fbx47


    de Assis, Leandro José and Ulas, Mevlut and Ries, Laure Nocolas Annick and El Ramli, Nadia Ali Mohamed and Bayram, Ozlem Sarikaya and Braus, Gerhard H. and Bayram, Ozgur and Goldman, Gustavo H. (2018) Regulation of Aspergillus nidulans CreA-Mediated Catabolite Repression by the F-Box Proteins Fbx23 and Fbx47. mBio, 9 (3). e00840-18. ISSN 2150-7511

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    Abstract

    The attachment of one or more ubiquitin molecules by SCF (Skp–Cullin–F-box) complexes to protein substrates targets them for subsequent degradation by the 26S proteasome, allowing the control of numerous cellular processes. Glucose-mediated signaling and subsequent carbon catabolite repression (CCR) are processes relying on the functional regulation of target proteins, ultimately controlling the utilization of this carbon source. In the filamentous fungus Aspergillus nidulans, CCR is mediated by the transcription factor CreA, which modulates the expression of genes encoding biotechnologically relevant enzymes. Although CreA-mediated repression of target genes has been extensively studied, less is known about the regulatory pathways governing CCR and this work aimed at further unravelling these events. The Fbx23 F-box protein was identified as being involved in CCR and the Δfbx23 mutant presented impaired xylanase production under repressing (glucose) and derepressing (xylan) conditions. Mass spectrometry showed that Fbx23 is part of an SCF ubiquitin ligase complex that is bridged via the GskA protein kinase to the CreA-SsnF-RcoA repressor complex, resulting in the degradation of the latter under derepressing conditions. Upon the addition of glucose, CreA dissociates from the ubiquitin ligase complex and is transported into the nucleus. Furthermore, casein kinase is important for CreA function during glucose signaling, although the exact role of phosphorylation in CCR remains to be determined. In summary, this study unraveled novel mechanistic details underlying CreA-mediated CCR and provided a solid basis for studying additional factors involved in carbon source utilization which could prove useful for biotechnological applications.

    Item Type: Article
    Additional Information: Copyright © 2018 de Assis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, https://creativecommons.org/licenses/by/4.0/ . Citation: Regulation of Aspergillus nidulans CreA-Mediated Catabolite Repression by the F-Box Proteins Fbx23 and Fbx47. Leandro José de Assis, Mevlut Ulas, Laure Nicolas Annick Ries, Nadia Ali Mohamed El Ramli, Ozlem Sarikaya-Bayram, Gerhard H. Braus, Ozgur Bayram, Gustavo Henrique Goldman mBio Jun 2018, 9 (3) e00840-18; DOI: 10.1128/mBio.00840-18
    Keywords: carbon catabolite repression; CreA; F-box; SCF complex; protein kinase;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 10999
    Identification Number: https://doi.org/10.1128/mBio.00840-18
    Depositing User: Ozgur Bayram
    Date Deposited: 29 Aug 2019 14:09
    Journal or Publication Title: mBio
    Publisher: American society for Microbiology
    Refereed: Yes
    URI:

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