SUMMARY PARAGRAPH for GCD2
Gcd2p is the delta subunit of the heteropentameric eukaryotic initiation factor 2B (eIF2B), which is required for translation initiation and its regulation in all eukaryotes (8, 9). Deletion of GCD2 is lethal, and mutations in GCD2 lead to slow growth and derepressed, or otherwise altered, translation. (3, 10, 11, 4, 1, 12).
eIF2B comprises a regulatory subcomplex composed of Gcd2p, Gcd7p, and Gcn3p, and a catalytic subcomplex containing Gcd1p and Gcd6p. 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 (8, 9, 13). The trimeric regulatory subcomplex does not possess guanine-nucleotide exchange activity, but interacts stably with eIF2 with a binding preference for phosphorylated eIF2 which, in its GDP-bound form, is an inhibitor of eIF2B (5, 14). Gcd2p, Gcd7p, and Gcn3p together mediate this inhibition of eIF2B activity by phosphorylated eIF2 (14).
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 (5). All five yeast subunits of eIF2B share extensive sequence similarity with their mammalian counterparts (5). 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) (15, 13).
Last updated: 2006-11-15