A role forcreD, a carbon catabolite repression gene fromAspergillus nidulans, in ubiquitination

Abstract

SummaryIn Aspergillus nidulans , it is known that creB encodes a deubiquitinating enzyme that forms a complex with the WD40 motif containing protein encoded by creC , that mutations in these genes lead to altered carbon source utilization and that the creD34 mutation suppresses the phenotypic effects of mutations in creC and creB . Therefore, creD was characterized in order to dissect the regulatory network that involves the CreB-CreC deubiquitination complex. CreD contains arrestin domains and PY motifs and is highly similar to the Rod1p and Rog3p proteins from Saccharomyces cerevisiae . An additional gene was identified in the A. nidulans genome that also encodes an arrestin and PY motif-containing protein, which we have designated apyA , and thus two similar proteins also exist in A. nidulans . In S. cerevisiae , Rod1p and Rog3p interact with the ubiquitin ligase Rsp5p, and so the A. nidulans homologue of Rsp5p was identified, and the gene encoding this HECT ubiquitin ligase was designated hulA . CreD and ApyA were tested for proteinprotein interactions with HulA via the bacterial twohybrid system, and ApyA showed strong interaction, and CreD showed weak interaction, with HulA in this system.

Regulation of the lignocellulolytic response in filamentous fungi

“…In N. crassa, VIB-1 is necessary for full cellulase and hemicellulase induction and appears to be an upstream regulator of genes involved in CCR, including cre-1 and the N. crassa homologs of two genes with potential roles in the ubiquitination pathway, creB and creD (Boase and Kelly, 2004;Hynes and Kelly, 1977;Kelly and Hynes, 1977;Lockington and Kelly, 2001;Xiong et al, 2014b). VIB-1 also regulates the expression of col-26, the N. crassa homolog of T. reesei bglR, a zinc binuclear cluster transcription factor that positively regulates glycosyl hydrolase expression (Nitta et al, 2012;Xiong et al, 2014b).…”

“…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.…”

Carbon source regulation of antibiotic production

“…The creD gene encodes a protein that contains arresting domains and PY motifs and interacts with the HECT (homologous to the E6-associated protein carboxyl terminus) ubiquitine ligase. 184 Although the elements of ubiquitination and deubiquitination networks have been disclosed, their direct targets still remain to be elucidated. 170 Recently, it was found that the mechanism of action of CreA in CCR does not require its degradation nor its cellular localization, but seems to entail some modification or interaction with another protein to act as a repressor.…”

α-Arrestins – new players in Notch and GPCR signaling pathways in mammals

“…a-Arrestins were first studied in fungi and yeast (see, for example, Andoh et al, 2002), even before being recognized as members of the arrestin clan (Boase and Kelly, 2004;Herranz et al, 2005). Saccharomyces cerevisiae has 11 a-arrestins but neither visual nor b-arrestins (Becuwe et al, 2012a); therefore, aarrestins are considered the ancestral factors of the arrestin family.…”