High impact information on GRR1

• GRR1 encodes the yeast F-box protein that is part of the SCF-GRR1 Ubiquitin proteolysis machinery that is required for regulating cell cycle in response to glucose signaling. [1]
• Surprisingly, one group of mutants was found to be allelic to GRR1, a gene previously described to be involved in glucose uptake, glucose repression, and divalent cation transport [2].
• This suggests that the GRR1 gene product is part of a common regulatory pathway linking two functions important for cell growth, nutrient uptake, and G1 cyclin-controlled cell division [2].
• The same mutations resulted in the stabilization of Cln2 and Gic2 and also in a spectrum of phenotypes characteristic of inactivation of GRR1, including hyperpolarization and enhancement of pseudohyphal growth [3].
• Strains that carry a COT2 allele conferring complete loss of function are viable and exhibit phenotypes similar to those of spontaneous cot2 mutations [4].
• The glucose dependence of the transport defect implies that cot2 mutations affect the link between glucose metabolism and divalent cation active transport [4].

Biological context of GRR1

• Principal components analysis of the summed fractional labelling data show that deleting the genes HXK2 and GRR1 results in similar phenotype at the fluxome level, with a partial alleviation of glucose repression on the respiratory metabolism [5].
• GRR1 protein contains 12 tandem repeats of a sequence similar to leucine-rich motifs found in other proteins that may mediate protein-protein interactions [6].
• The combined genetic and molecular data are consistent with the idea that GRR1 protein is a primary response element in the glucose repression pathway and is required for the generation or interpretation of the signal that induces glucose repression [6].
• Deletion of GRR1 from the C. albicans genome results in a highly filamentous, pseudohyphal morphology under conditions that normally promote the yeast form of growth [7].
• The function of either gene product seems to be more important in metal homeostasis than is the GRR1 gene product, which is also involved in metal metabolism [8].

Associations of GRR1 with chemical compounds

• GRR1 seems to encode a positive regulator of HXT expression, since grr1 mutants are defective in glucose induction of all four HXT genes [9].
• Overexpression in GRR1 cells resulted in sulfite sensitivity, suggesting a connection between CLN1 and sulfite metabolism [10].
• Comparison of the grr1Delta strain with the reference strain in the absence of citrulline revealed that GRR1 disruption leads to increased transcription of numerous genes [11].

Other interactions of GRR1

• GRR1 protein interacts with SKP1 protein. Along with CDC53 protein, they form the yeast SCF-GRR1 ubiquitin conjugating ligase complex [1]
• RGT2 and GRR1 also play a role in regulating the expression of the HXT genes, which appear to be the upstream components of the glucose-transport-dependent pathway regulating maltose permease inactivation [12].
• New SNF genes, GAL11 and GRR1 affect SUC2 expression in Saccharomyces cerevisiae [13].
• These mutations, designated generically elm (elongated morphology), defined 14 genes; two of these corresponded to the previously described genes GRR1 and CDC12 [14].
• These findings suggest that GRR1 and SNF3 affect glucose transport by distinct pathways [15].
• Multicopy suppression analysis, undertaken to explore relationships among genes previously implicated in sulfite metabolism, suggests a regulatory pathway in which SSU1 acts downstream of FZF1 and SSU3, which in turn act downstream of GRR1 [16].

Analytical, diagnostic and therapeutic context of GRR1

• Indeed, cell fractionation studies are consistent with this view, suggesting that GRR1 protein is tightly associated with a particulate protein fraction in yeast extracts [6].

References