Gcd1p is the gamma subunit of the heteropentameric eukaryotic initiation factor 2B (eIF2B), which is required for translation initiation and its regulation in all eukaryotes (6, 7). eIF2B comprises a catalytic subcomplex containing Gcd1p and Gcd6p, and a regulatory subcomplex composed of Gcd2p, Gcd7p, and Gcn3p. As the guanine nucleotide exchange factor for translation initiation factor eIF2, eIF2B recycles eIF2 from a GDP- to a GTP-bound form that is competent for translation initiation, a key control point for translation (6, 7, 8). The formation of the catalytic Gcd1p-Gcd6p subcomplex serves to stabilize the interaction of Gcd6p, which possesses the actual guanine nucleotide exchange activity, with eIF2, thereby enhancing its nucleotide-exchange activity (3). Mutations in GCD1 lead to derepressed translation (9, 10) or otherwise altered translational control (11, 12), as well as lack of growth at high temperatures because cells cannot proceed beyond START of the cell division cycle (13).

eIF2B is found in a specific cytoplasmic focus in yeast, with eIF2 shuttling back and forth, implicating this cytoplasmic focus as a site of guanine nucleotide exchange. eIF2B activity is inhibited in response to starvation or stress by phosphorylation of the alpha subunit of eIF2 (3). All five yeast subunits of eIF2B share extensive sequence similarity with their mammalian counterparts (3). Mutations in any of the five human subunits cause a fatal disease called CACH (childhood ataxia with central nervous system hypomyelination) or VWM (vanishing white matter disease) (14, 8).

Last updated: 2006-11-15