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Gene Review

GCD2  -  Gcd2p

Saccharomyces cerevisiae S288c

Synonyms: GCD complex subunit GCD2, Guanine nucleotide exchange factor subunit GCD2, TIF224, Translation initiation factor eIF-2B subunit delta, YGR083C, ...
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Disease relevance of GCD2

  • Overexpressing only GCD2 and GCD7 also reduced eIF2(alphaP) toxicity, presumably by titrating GCN3 from eIF2B and producing the four-subunit form of eIF2B that is less sensitive to eIF2(alphaP) [1].

High impact information on GCD2

  • These results imply that structurally similar segments in GCD2, GCD7, and GCN3 perform related functions in eIF2B regulation [2].
  • Together, our results provide strong evidence that GCN3, GCD7, and the C-terminal half of GCD2 comprise the regulatory domain in eIF2B [1].
  • This interpretation is supported by the fact that overexpressing GCD2 and GCD7 did not reduce eIF2(alphaP) toxicity in a strain lacking GCN3; however, it did suppress the impairment of eIF2B caused by the gcn3c-R104K mutation [1].
  • 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 [3].
  • We present evidence that GCD2 has a general function in the initiation of protein synthesis in addition to its gene-specific role in translational control of GCN4 expression [4].

Biological context of GCD2

  • We propose that GCD7 and GCD2 play important roles in the regulatory interaction between eIF-2 and eIF-2B and that the suppressor mutations we isolated in these genes decrease the susceptibility of eIF-2B to the inhibitory effects of phosphorylated eIF-2 without impairing the essential catalytic function of eIF-2B in translation initiation [5].
  • The amino acid sequence changes for three gcd2 mutations have been determined, and we describe several examples of mutual suppression involving the gcd2 mutations and particular alleles of GCN3 [3].
  • We demonstrate that GCD12 and GCD2 are the same genes; however, unlike gcd12 mutations, the growth defect and constitutive derepression phenotypes associated with the gcd2-1 mutation are expressed in the presence of the wild-type GCN3 gene [6].
  • GCD2 is also required unconditionally for cell viability [7].
  • The GCD12 gene has been cloned and mapped to the right arm of chromosome VII, very close to the map position reported for GCD2 [6].

Associations of GCD2 with chemical compounds

  • Both threonine deaminase activity and ILV1 mRNA levels increase in mutants (gcd2 and gcd3) having constitutively depressed levels of enzymes under the general control of amino acid biosynthesis, as well as in response to starvation for tryptophan and branched-chain amino acid imbalance [8].

Physical interactions of GCD2

  • Interestingly, a portion of the eIF-2 present in cell extracts also cofractionated and coimmunoprecipitated with these regulatory proteins but was dissociated from the GCD1/GCD2/GCN3 complex by 0.5 M KCl [9].

Regulatory relationships of GCD2

  • This observation suggests that GCN3 can promote or at least partially substitute for GCD2 function in normal growth conditions, while acting as an antagonist of GCD2 in amino acid starvation conditions [7].
  • The GCD2 gene product is required in conditions of amino acid sufficiency to repress the synthesis of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae [7].

Other interactions of GCD2

  • These allele-specific interactions have led us to propose that GCN3 and GCD2 directly interact in the GCD-eIF-2B complex [3].
  • The three proteins copurified through several biochemical fractionation steps and could be coimmunoprecipitated by using antibodies against GCD1 or GCD2 [9].
  • gcd12 mutations are gcn3-dependent alleles of GCD2, a negative regulator of GCN4 in the general amino acid control of Saccharomyces cerevisiae [6].
  • Complementation tests amongst the four new gcd-mutant strains, including strain RH558 gcd2-1 isolated earlier, yielded five complementation groups: GCD2, GCD3, GCD4, GCD5, and GCD6 [10].


  1. Identification of a regulatory subcomplex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF2. Yang, W., Hinnebusch, A.G. Mol. Cell. Biol. (1996) [Pubmed]
  2. Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF2. Pavitt, G.D., Yang, W., Hinnebusch, A.G. Mol. Cell. Biol. (1997) [Pubmed]
  3. 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]
  4. GCD2, a translational repressor of the GCN4 gene, has a general function in the initiation of protein synthesis in Saccharomyces cerevisiae. Foiani, M., Cigan, A.M., Paddon, C.J., Harashima, S., Hinnebusch, A.G. Mol. Cell. Biol. (1991) [Pubmed]
  5. Mutations in the GCD7 subunit of yeast guanine nucleotide exchange factor eIF-2B overcome the inhibitory effects of phosphorylated eIF-2 on translation initiation. Vazquez de Aldana, C.R., Hinnebusch, A.G. Mol. Cell. Biol. (1994) [Pubmed]
  6. gcd12 mutations are gcn3-dependent alleles of GCD2, a negative regulator of GCN4 in the general amino acid control of Saccharomyces cerevisiae. Paddon, C.J., Hinnebusch, A.G. Genetics (1989) [Pubmed]
  7. Amino acid sequence similarity between GCN3 and GCD2, positive and negative translational regulators of GCN4: evidence for antagonism by competition. Paddon, C.J., Hannig, E.M., Hinnebusch, A.G. Genetics (1989) [Pubmed]
  8. Regulation of isoleucine-valine biosynthesis in Saccharomyces cerevisiae. Holmberg, S., Petersen, J.G. Curr. Genet. (1988) [Pubmed]
  9. Complex formation by positive and negative translational regulators of GCN4. Cigan, A.M., Foiani, M., Hannig, E.M., Hinnebusch, A.G. Mol. Cell. Biol. (1991) [Pubmed]
  10. Identification and characterization of four new GCD genes in Saccharomyces cerevisiae. Niederberger, P., Aebi, M., Hütter, R. Curr. Genet. (1986) [Pubmed]
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