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GCD1  -  Gcd1p

Saccharomyces cerevisiae S288c

Synonyms: GCD complex subunit GCD1, Guanine nucleotide exchange factor subunit GCD1, TIF223, TRA3, Translation initiation factor eIF-2B subunit gamma, ...
 
 
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High impact information on GCD1

  • Such an increase is effected when the cellular amount of the GCN2 protein kinase is increased or when the function of the GCD1 gene product is defective [1].
  • In contrast, the GCD1 and GCD6 subunits form an eIF2B subcomplex that binds equally to eIF2 and eIF2(alphaP) [2].
  • Using genetic mapping, we have identified a proline to serine allelic variation at amino acid 180 of the GCD1 gene product as the genetic locus that allows translational regulation upon butanol addition [3].
  • Gcd1p forms part of the eIF2B guanine nucleotide complex that is responsible for recycling eIF2-GDP to eIF2-GTP [3].
  • Either aas1- or aas2- in combination with tra3- has the Tra- phenotype, whereas aas3- in combination with tra3- has the Aas- phenotype [4].
 

Biological context of GCD1

  • A deletion of four small open reading frames in the 5' leader of GCN4-lacZ mRNA mimicked the effect of a gcd1 mutation and derepressed translation of the fusion transcript in the absence of either starvation conditions or the GCN2 and GCN3 products [5].
  • These data suggest that GCN3, GCD1 and GCD12 have closely related functions required for regulation of GCN4 expression and entry into the cell cycle [6].
  • We have cloned and sequenced the GCD1 gene and examined various aspects of cellular metabolism in order to elucidate its role(s) in regulating gene expression and the cell cycle [7].
  • GCD1 may also be part of a sensing mechanism in which cells monitor the protein synthesis capacity prior to initiating a new cell division cycle [7].
  • GCD1 is an essential gene because cells containing a gcd1-HIS3 disruption are unable to grow [7].
 

Associations of GCD1 with chemical compounds

  • Previous genetic and biochemical experiments led to the conclusion that GCD1, GCD2, and GCN3 are components of the GCD complex, recently shown to be the yeast equivalent of the mammalian guanine nucleotide exchange factor for eIF-2, known as eIF-2B [8].
  • In the absence of adenine in the medium ADE2 gene expression is derepressed, and neither starvation for histidine nor a gcd1 general control regulatory mutation leads to additional derepression [9].
 

Regulatory relationships of GCD1

  • The GCD1 product appears to inhibit translation of GCN4 mRNA because under certain growth conditions, the gcd1-101 mutation led to derepression of the GCN4-lacZ fusion enzyme level in the absence of any increase in the fusion transcript level [5].
  • A gcn3 deletion leads to unconditional lethality in a gcd1-101 mutant, supporting the idea that GCN3 is expressed under normal growth conditions and cooperates with the GCD1 product under these circumstances to carry out an essential cellular function [10].

References

  1. Coupling of GCN4 mRNA translational activation with decreased rates of polypeptide chain initiation. Tzamarias, D., Roussou, I., Thireos, G. Cell (1989) [Pubmed]
  2. eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and regulate guanine-nucleotide exchange. Pavitt, G.D., Ramaiah, K.V., Kimball, S.R., Hinnebusch, A.G. Genes Dev. (1998) [Pubmed]
  3. A novel eIF2B-dependent mechanism of translational control in yeast as a response to fusel alcohols. Ashe, M.P., Slaven, J.W., De Long, S.K., Ibrahimo, S., Sachs, A.B. EMBO J. (2001) [Pubmed]
  4. Positive regulation in the general amino acid control of Saccharomyces cerevisiae. Hinnebusch, A.G., Fink, G.R. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  5. A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Hinnebusch, A.G. Mol. Cell. Biol. (1985) [Pubmed]
  6. Interactions between positive and negative regulators of GCN4 controlling gene expression and entry into the yeast cell cycle. Harashima, S., Hannig, E.M., Hinnebusch, A.G. Genetics (1987) [Pubmed]
  7. Molecular characterization of GCD1, a yeast gene required for general control of amino acid biosynthesis and cell-cycle initiation. Hill, D.E., Struhl, K. Nucleic Acids Res. (1988) [Pubmed]
  8. Guanine nucleotide exchange factor for eukaryotic translation initiation factor 2 in Saccharomyces cerevisiae: interactions between the essential subunits GCD2, GCD6, and GCD7 and the regulatory subunit GCN3. Bushman, J.L., Foiani, M., Cigan, A.M., Paddon, C.J., Hinnebusch, A.G. Mol. Cell. Biol. (1993) [Pubmed]
  9. Control of the expression of the ADE2 gene of the yeast Saccharomyces cerevisiae. Gedvilaite, A., Sasnauskas, K. Curr. Genet. (1994) [Pubmed]
  10. Molecular analysis of GCN3, a translational activator of GCN4: evidence for posttranslational control of GCN3 regulatory function. Hannig, E.M., Hinnebusch, A.G. Mol. Cell. Biol. (1988) [Pubmed]
 
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