High impact information on GCN1

• Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid-starved cells [1].
• We conclude that binding of GCN1-GCN20 to GCN2 is required for its activation by uncharged tRNA [2].
• GCN1 expression conferred sensitivity to paromomycin in a manner dependent on its ribosome binding domain, supporting the idea that GCN1 binds near the ribosomal acceptor site to promote GCN2 activation by uncharged tRNA [1].
• Overexpression of this fragment in wild-type cells impaired association of GCN2 with native GCN1 and had a dominant Gcn(-) phenotype, dependent on Arg2259 in the GCN1 fragment [1].
• At odds with this idea, indirect immunofluorescence revealed cytoplasmic localization of GCN1 and no obvious association with plasma or vacuolar membranes [3].

Biological context of GCN1

• We show that this key phosphorylation event and the attendant translational induction of GCN4 are dependent on the product of a previously uncharacterized gene, GCN1 [4].
• Furthermore, a gcd3 mutation can overcome the derepression-deficient phenotype of mutations in the positive regulatory GCN1, GCN2, and GCN3 genes [5].
• We describe point mutations in two conserved, noncontiguous segments of GCN1 that lead to reduced polyribosome association by GCN1.GCN20 in living cells without reducing GCN1 expression or its interaction with GCN20 [6].
• An analysis of a class A auxotroph revealed that it lacked L-glutamine:D-fructose 6-phosphate amidotransferase (EC 2.6.1.16) activity and indicates that GCN1 codes the amino acid sequence of this enzyme [7].
• Diploids homozygous for gcn1 fail to complete sporulation [7].

Anatomical context of GCN1

• This sequence similarity raises the possibility that GCN1 interacts with ribosomes or tRNA molecules and functions in conjunction with GCN2 in monitoring uncharged tRNA levels during the process of translation elongation [4].
• Polyribosome binding by GCN1 is required for full activation of eukaryotic translation initiation factor 2{alpha} kinase GCN2 during amino acid starvation [6].

Associations of GCN1 with chemical compounds

• Yeast strains bearing a mutation in any one of the genes GCN1 to GCN4 are defective in derepression of amino acid biosynthetic genes in 10 different pathways under conditions of histidine limitation [8].
• The same conclusion was reached independently by an investigation of spores of a strain homozygous for the mutation gcn1, which lack the outermost layers of the spore wall and were practically devoid of dityrosine [9].

Physical interactions of GCN1

• A C-terminal segment of GCN1 (residues 2052-2428) was found to be necessary and sufficient for binding GCN2 in vivo and in vitro [1].

Other interactions of GCN1

• Mutation of other components of this regulatory circuit such as GCN1 and GCN3 also resulted in improved NaCl tolerance [10].
• Thus, we may have identified a new class of GCN genes which are functionally distinct from GCN1 through GCN5 [11].
• This conclusion supports the model that an eEF3-related activity of GCN1 influences occupancy of the ribosomal decoding site by uncharged tRNA in starved cells [6].
• The gene (the gene should be called GFA1 for glutamine:fructose-6-phosphate amidotransferase) for the enzyme has been cloned by complementing the gcn1 mutation (Whelan, W. L., and Ballou, C. E. (1975) J. Bacteriol. 125, 1545-1557) [12].

References