Academic journal article Genetics

Diverse Regulation of the CreA Carbon Catabolite Repressor in Aspergillus Nidulans

Academic journal article Genetics

Diverse Regulation of the CreA Carbon Catabolite Repressor in Aspergillus Nidulans

Article excerpt

GLUCOSE is the preferred carbon source for most microorganisms. Selecting the most energetically favorable carbon source is a survival strategy for microorganisms because it supports the rapid growth and development required for colonizing diverse habitats (Ruijter and Visser 1997). This process of carbon source selection is known as carbon catabolite repression (CCR). In the filamentous fungus Aspergillus nidulans, CCR is mediated by the transcription factor CreA, aC2H2 DNA-binding protein (Dowzer and Kelly 1991). On glucose detection, genes encoding enzymes (e.g., xylanases, cellulases, and arabinases) required for the breakdown of alternative carbon sources, such as lignocellulose, are repressed. This is a disadvantage for second-generation (2G) biofuel production that aims to convert nonglucose saccharides (e.g., xylose, arabinose, and cello- and xylooligosaccharides) to biofuels from lignocellulosic plant mass. In A. nidulans,CreA directly represses xylanases encoded by xlnA and xlnD via binding to the consensus DNA sequence 59-SYGGRG-39 in the promoter regions of these genes (Tamayo et al. 2008). The expression of xlnR, encoding the main inducer of xylanase and, to some extent, cellulase-encoding genes, is also under CreA regulatory control (Tamayo et al. 2008). Thus, CreA also indirectly represses all the genes that are under the regulatory influence of XlnR. Furthermore, CreA also represses genes involved in arabinose utilization (Ruijter and Visser 1997). Roy et al. (2008) previously described four different regions in CreA (Figure1).CreAcontainstw°C2H2-type zinc fingers required for DNA binding followed by a region containing seven alanine residues. Similar to Trichoderma reesei, the N-terminal part of CreA contains an acidic amino acid-rich region that is located adjacent to a highly conserved region among A. nidulans, A. niger, and T. reesei. This conserved region is followed by a region shown to be essential for repression. Apart from the region important for mediating repression, the other three regions described have yet to be characterized. Previous studies (Ruijter and Visser 1997; Tamayo et al. 2008) investigated the repressive role of CreA at the transcriptional level in controlling the expression of genes encoding enzymes required for lignocellulose degradation. Yet few studies have examined how CreA is transcriptionally and post-translationally regulated.

Expression of creA was proposed to be autoregulated because CreA-binding sequences are present within its promoter region (Arst et al. 1990; Schroff et al. 1996; Strauss et al. 1999). Furthermore, regulation of CreA is thought to occur via the removal of ubiquitin molecules from the protein that leads to active CreA, a process that may be mediated by the CreB-CreC deubiquitination (DUB) complex (Lockington and Kelly 2002). CreB is a ubiquitin-specific processing (UBP) family protease that functions downstream of CreC; the latter is a WD-40 domain protein required for CreB stabilization (Lockington and Kelly 2002). Deubiquitinating enzymes are cysteine proteases that target the activation domains of specific transcription factors. Ubiquitination serves as a marker on proteins for targeting them to the proteasome, for macromolecular assembly, or for altering protein function (Lockington and Kelly 2002). DUB enzymes also interact with ubiquitin ligases, and together they likely control the amounts of transcription factors present during CCR (Kubicek et al. 2009). The CreB-CreC DUB complex has been proposed to be involved in CCR because mutations in CreB and CreC alleviate CCR (Hynes and Kelly 1977). Deletion of creB and cre2 in A. oryzae and T. reesei, respectively, resulted in elevated levels of secreted hydrolytic enzymes (Denton and Kelly 2011; Hunter et al. 2013). Furthermore, recent studies have indicated that FbxA, a protein involved in ubiquitination of target proteins, is involved in creA messenger RNA (mRNA) accumulation (Colabardini et al. 2012). …

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