Hemin-independent control of globin synthesis in Friend erythroleukemia cells induced to differentiate

Abstract

A hemin-independent translational inhibitor that prevents synthesis of rabbit globin when uninduced Friend leukemia (FL) cell and rabbit reticulocyte lysates are mixed [Cimadevilla, J. M. & Hardesty, B. (1975) Biochem. Biophys. Res. Commun. 63, 931-937] cannot be detected in FL cells induced to differentiate. Mixing of lysates of FL cells induced with hexamethylene bisacetamide or aminonucleoside of puromycin and rabbit reticulocytes does not cause inhibition of rabbit globin synthesis. Induction also results in the cells acquiring sensitivity to the inhibitor from uninduced FL cells. A reduction in total protein synthesis is observed when uninduced and induced FL cell lysates are mixed. Inhibition does not result from competition by an excess of uninduced FL cell mRNA species for the translational machinery because uninduced FL cell lysates retain their inhibitory activity after treatment with micrococcal nuclease. Rabbit globin mRNA recovered from rabbit reticulocyte lysates that have been incubated with lysates of uninduced FL cells can still be translated effectively, indicating that inhibition does not result from modification of other species of mRNA by uninduced FL cell lysates. A switch to hemin-dependent translational control does not follow induction of differentiation. The rate of amino acid incorporation in induced FL cell lysates--like that in uninduced FL cell lysates--is unaffected by omission of exogenous hemin from the system. Its presence is not required to prevent activation of heme-regulated inhibitor. From these data, it is clear that the control of protein synthesis in FL cells--whether or not they are induced--is different from that regulated by hemin in normal erythroid cells.