Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle

Abstract

Grr1 protein of the yeast Saccharomyces cerevisiae is a central component of a glucose signal transduction mechanism responsible for glucose-induced gene expression. It is required for glucose-stimulated regulation of Rgt1, a repressor of several glucose-induced HXT genes. Grr1 also plays a role in regulating the cell cycle, because it is required for degradation of the G1 cyclins Cln1 and Cln2. We discovered that Grr1 physically interacts with Skp1, a protein that has been implicated in a ubiquitin-conjugating enzyme complex that targets for degradation the cell cycle regulators Cln1 and Cln2, and the cyclin-dependent kinase inhibitor Sic1. Thus, Grr1 may regulate the cell cycle and glucose-induced gene expression via ubiquitin-mediated protein degradation. Consistent with this idea, Skp1, like Grr1, was found to be required for glucose-induced HXT gene expression. Two functional domains of Grr1 are required for its interaction with Skp1: 12 leucine-rich repeats (LRR) and an adjacent F-box. The Grr1-Skp1 interaction is enhanced by high levels of glucose. This could provide yeast with a mechanism for coupling nutrient availability to gene expression and cell cycle regulation.