A protein complex of translational regulators of GCN4 mRNA is the guanine nucleotide-exchange factor for translation initiation factor 2 in yeast

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-06, Vol.90 (11), p.5350-5354
• Main Authors: Cigan, A.M, Bushman, J.L, Boal, T.R, Hinnebusch, A.G
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Antibodies; Antigen antibody complex; Biochemistry; Biological and medical sciences; Chromatography, Affinity; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Epitopes; Eukaryotic Initiation Factor-2 - isolation & purification; Eukaryotic Initiation Factor-2 - metabolism; Eukaryotic Initiation Factor-2B; FENOTIPOS; Fundamental and applied biological sciences. Psychology; Fungal Proteins - biosynthesis; Fungal Proteins - genetics; Fungal Proteins - isolation & purification; Fungal Proteins - metabolism; Gene Expression Regulation, Fungal; Genetic mutation; GENETICA MOLECULAR; GENETIQUE MOLECULAIRE; Guanine Nucleotide Exchange Factors; Guanine nucleotides; Guanosine Triphosphate - metabolism; Kinetics; LEVADURA; LEVURE; Messenger RNA; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; MUTACION; MUTATION; NUCLEOTIDE; NUCLEOTIDOS; PHENOTYPE; Phosphorylation; PLASMIDE; PLASMIDIOS; Protein Biosynthesis; Protein Kinases - biosynthesis; Protein Kinases - genetics; Proteins; Repressor Proteins - genetics; Repressor Proteins - isolation & purification; Repressor Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Transfer, Amino Acyl - metabolism; RNA, Transfer, Met; SACCHAROMYCES CEREVISIAE; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Translation. Translation factors. Protein processing; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.11.5350

In Saccharomyces cerevisiae, phosphorylation of the a subunit of translation initiation factor 2 (eIF-2) by protein kinase GCN2 stimulates translation of GCN4 mRNA. In mammalian cells, phosphorylation of eIF-2 alpha inhibits the activity of eIF-2B, the GDP-GTP exchange factor for eIF-2. We present biochemical evidence that five translational regulators of GCN4 encoded by GCD1, GCD2, GCD6, GCD7, and GCN3 are components of a protein complex that stably interacts with eIF-2 and represents the yeast equivalent of eIF-2b. In vitro, this complex catalyzes guanine nucleotide exchange on eIF-2 and overcomes the inhibitory effect of GDP on formation of eIF-2-GTP-Met-initiator tRNA(Met) ternary complexes. This finding suggests that mutations in GCD-encoded subunits of the complex derepress GCN4 translation because they mimic eIF-2 alpha phosphorylation in decreasing eIF-2B activity. Our results indicate that translational control of GCN4 involves a reduction in eIF-2B function, a mechanism used in mammalian cells to regulate total protein synthesis in response to stress