Translational initiation factor expression and ribosomal protein gene expression are repressed coordinately but by different mechanisms in murine lymphosarcoma cells treated with glucocorticoids.
P1798 murine lymphosarcoma cells cease to proliferate upon exposure to 10(-7) M dexamethasone and exhibit a dramatic inhibition of rRNA and ribosomal protein synthesis (O. Meyuhas, E. Thompson, Jr., and R. P. Perry, Mol. Cell Biol. 7:2691-2699, 1987). These workers demonstrated that ribosomal protein synthesis is regulated primarily at the level of translation, since dexamethasone did not alter mRNA levels but shifted the mRNAs from active polysomes into inactive messenger ribonucleoproteins. We have examined the effects of dexamethasone on the biosynthesis of initiation factor proteins in the same cell line. The relative protein synthesis rates of eIF-4A and eIF-2 alpha were inhibited by about 70% by the hormone, a reduction comparable to that for ribosomal proteins. The mRNA levels of eIF-4A, eIF-4D, and eIF-2 alpha also were reduced by 60 to 70%, indicating that synthesis rates are proportional to mRNA concentrations. Analysis of polysome profiles showed that the average number of ribosomes per initiation factor polysome was only slightly reduced by dexamethasone, and little or no mRNA was present in messenger ribonucleoproteins. The results indicate that initiation factor gene expression is coordinately regulated with ribosomal protein synthesis but is controlled primarily by modulating mRNA levels rather than mRNA efficiency.
Department of Biological Chemistry, School of Medicine, University of California, Davis 95616.
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Huang
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JW
Hershey
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D009363:Neoplasm Proteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012269:Ribosomal Proteins; D003907:Dexamethasone