GROWTH-DEPENDENT AND PKC-MEDIATED TRANSLATIONAL REGULATION OF THE UPSTREAM STIMULATING FACTOR-II (USF2) MESSENGER-RNA IN HEMATOPOIETIC-CELLS

Upstream stimulating factor (USF2) is a basic helix-loop-helix leucine zipper transcription factor, which is found in most tissues, A critic al role for USF2 in cellular proliferation has been proposed based on its importance in the regulation of various cyclins and P53 and its ca pability to antagonize c-myc., In this paper we report that IL-3, whic h is a major growth factor for mast cells, induces USF2 protein synthe sis in murine mast cells (MC-9), Surprisingly, it does not significant ly affect the level of USF2 mRNA in these cells at any of the time poi nts tested, Using polysomal fractionation and RNA analysis we then dem onstrated that this translational regulation is mostly the result of i ncreased USF2 translational efficiency. Moreover, protein kinase C (PK C) inhibitors prevented both the induction of USF2 protein synthesis a nd the increase in USF2 translational efficiency in IL-3-activated mas t cells, Two other hematopoietic cell lines were used to determine whe ther the translational regulation of USF2 is of a more general nature: mouse lymphosarcoma cells whose proliferation is inhibited by dexamet hasone; and mouse erythroleukemia cells that differentiate upon exposu re to hexamethylen bisacetamide, In both cell types, USF2 translation was repressed in the non-dividing cells, This strongly implies that US F2 is translationally repressed in quiescent hematopoietic cells, Cons idering the proposed role of USF in proliferation it seems that transl ational regulation of USF2 might have an important role in cellular gr owth.