Regulation of the Gid ubiquitin ligase recognition subunit Gid4.

Abstract

Glucose consumption via glycolysis and its biosynthesis via gluconeogenesis are central reciprocal pathways controlled by a set of different enzymes. In the yeast Saccharomycescerevisiae, expression of gluconeogenic enzymes is induced when cells are devoid of glucose. Availability of glucose immediately leads to inactivation and rapid degradation of these enzymes via the ubiquitin proteasome system. Polyubiquitination is carried out by the Gid complex, a multisubunit RING E3 ligase that constitutively consists of six different proteins. Upon addition of glucose to the medium, the substrate recognition subunit Gid4 appears within minutes and triggers ubiquitination of the gluconeogenic enzymes. Here, we show that Gid4 is tightly regulated on the transcriptional and protein level to ensure proper adjustment of gluconeogenesis.