Inhibition of polypeptide synthesis by a factor isolated from ribosomes of resting human lymphocytes: Studies on the mechanism of action

Abstract

Peripheral blood lymphocytes are non-dividing cells which synthesize small amounts of RNA and protein. These resting cells are stimulated when incubated in the presence of mitogens, and after a variety of metabolic changes which include a marked increase of RNA and protein synthesis, they start DNA replication and reach a state of active proliferation [ 1,2]. The enhancement of protein synthesis occurring during the first hours after the addition of PHA to a lymphocyte culture does not require the synthesis of RNA 13-51, indicating that during this period preexisting mRNA molecules and ribosomal particles are being utilized. Thus lymphocyte activation may involve regulation at the translational level besides other controls which might be occurring on transcription and DNA replication. Experiments with cell-free systems have indicated that the low rate of protein synthesis observed in unstimulated lymphocytes is probably due to the absence of initiation factors [6] and/or to the presence of cytoplasmic inhibitors which block the formation of initiation complexes [7,8]. The possibility of a more complex control of protein synthesis in lymphocytes has been reinforced by the isolation of a new ribosome-bound translational inhibitor (TI) obtained from resting human lymphocytes [9].