REGULATION OF EUKARYOTIC TRANSLATION

PHOSPHORYLATION & DEPHOSPHORYLATION

 Phosphorylation & Dephosphorylation are the biological switches that regulate the activity of biomolecules. Translation in eukaryotes is regulated via phosphorylation & dephosphorylation of eIF-2. Translation in reticulocytes (which is devoted to synthesis of hemoglobin) is controlled by the supply of heme, which regulates the activity of eIF-2.The active form of eIF-2 (complexed with GTP) escorts initiator methionyl tRNA to the ribosome The eIF-2 is then released from the ribosome in an inactive GDP-bound form, which must be reactivated by exchange of GTP for the bound GDP. If adequate heme is available, this exchange occurs and translation is able to proceed. If heme supplies are inadequate, however, a protein kinase named heme-regulated inhibitor[HRI] that phosphorylates eIF-2 is activated. Phosphorylation of eIF-2 blocks the exchange of GTP for GDP, so eIF2/GTP cannot be regenerated and translation is inhibited.

eIF-2 regulation

 The phosphorylated eIF-2 molecules can be reactivated by the action of eIF-2 phosphatase by dephosphorylation. eIF-2----P + eIF-2 phosphatase + water -----eIF-2 + Pi

Similar mechanisms have been found to control protein synthesis in other cell types, particularly virus-infected cells in which viral protein synthesis is inhibited by interferon.involves modulation of the activity of initiation factors, particularly eIF-2.