Diverse Regulation of the CreA Carbon Catabolite Repressor in Aspergillus nidulans

Abstract

Carbon catabolite repression (CCR) is a process that selects the energetically most favorable carbon source in an environment. CCR represses the use of less favorable carbon sources when a better source is available. Glucose is the preferential carbon source for most microorganisms because it is rapidly metabolized, generating quick energy for growth. In the filamentous fungus Aspergillus nidulans, CCR is mediated by the transcription factor CreA, a C 2 H 2 finger domain DNA-binding protein. The aim of this work was to investigate the regulation of CreA and characterize its functionally distinct protein domains. CreA depends in part on de novo protein synthesis and is regulated in part by ubiquitination. CreC, the scaffold protein in the CreB-CreC deubiquitination (DUB) complex, is essential for CreA function and stability. Deletion of select protein domains in CreA resulted in persistent nuclear localization and target gene repression. A region in CreA conserved between Aspergillus spp. and Trichoderma reesei was identified as essential for growth on various carbon, nitrogen, and lipid sources. In addition, a role of CreA in amino acid transport and nitrogen assimilation was observed. Taken together, these results indicate previously unidentified functions of this important transcription factor. These novel functions serve as a basis for additional research in fungal carbon metabolism with the potential aim to improve fungal industrial applications.

Regulation of the lignocellulolytic response in filamentous fungi

“…For example, the TOR complex is involved in nutrient sensing in eukaryotes and has been shown to be highly phosphorylated under cellulolytic conditions in N. crassa (Wullschleger et al, 2006;Xiong et al, 2014a). Putative ubiquitination and deubiquitination enzymes, such as CreB/CRE-2 and CreD, have been implicated in CCR and glycosyl hydrolase production potentially through ubiquitination of CreA itself, however, additional protein targets and the precise mechanism of action of the genes involved has yet to be identified (Boase and Kelly, 2004;Colabardini et al, 2012;Denton and Kelly, 2011;Kelly, 2001, 2002;Ries et al, 2016;Xiong et al, 2014b). The elucidation of the role of these and other highly conserved actors like the AMP-activated kinase, SnfA/SNF1, in the repression of plant cell wall degrading enzymes could help illuminate the regulation of transcription under cellulolytic conditions as well as nutrient-sensing pathways in eukaryotic species.…”

Nuclear export‐dependent degradation of the carbon catabolite repressor CreA is regulated by a region located near the C‐terminus in Aspergillus oryzae

“…The function of these factors has led us to the hypothesis that proteolytic degradation of the CreA protein is involved in CCR regulation. This hypothesis is supported by recent studies that describe the detection of a proteolytic degradation product of green florescent protein (GFP)‐fused A. nidulans CreA and T. reesei CRE1 (Lichius et al, ; Ries et al, ).…”

“…). In A. nidulans , both intact and nuclear‐retained truncated CreA were released from DNA following incubation in a medium supplemented with sugarcane bagasse (Ries et al, ). These observations suggest that nuclear export and degradation of CreA are not required for the release of CreA bound to the promoter region of carbon catabolite‐repressible genes.…”

“…A). In A. nidulans , CreA‐GFP protein was not detectable in the creC mutant strain, whereas the CreA‐GFP protein level in the creB mutant strain was comparable to that in the wild‐type strain (Ries et al, ). Because the A. nidulans stain used to express CreA‐GFP contained the creB allele ( creB15 ), which had a mutation comprising a single amino acid substitution, we hypothesize that this mutation is not sufficient to abrogate the reduction in the level of CreA protein.…”

Transient In Vivo Resistance Mechanisms of Burkholderia pseudomallei to Ceftazidime and Molecular Markers for Monitoring Treatment Response

“…BP1026B_I1021 is a putative regulator of the nar -operon that encodes a respiratory nitrate reductase, which is known to be associated with denitrification and anaerobic nitrite respiration. BP1026B_I0763 encodes a hypothetical LysR-type transcriptional regulator family, which has been shown to be involved in regulation of diverse sets of genes involved in adaptive metabolism and virulence [26], and BP1026B_I0849 encodes a hypothetical protein containing the CreA regulatory domain, which is associated with a transcriptional regulator component of the regulatory domain controlling carbon source utilization [27]. …”