Posttranscriptional changes in growth factor-inducible gene regulation caused by antiproliferative interferons.
Growth factors stimulate quiescent fibroblasts to progress through G0/G1, in part by inducing the expression of genes whose products are necessary or permissive for cell proliferation. Interferons, by contrast, inhibit progress through G0/G1 by mechanisms that are poorly understood. We show, in BALB/c murine 3T3 fibroblasts (A31 cells), that alpha/beta-interferon (IFN) had no effect the growth factor-dependent induction of several messenger ribonucleic acids (mRNAs), including those encoding ornithine decarboxylase (odc), fibronectin and the c-fos and c-myc protooncogenes. However, IFN caused an abnormal accumulation of fibronectin and c-myc mRNA on polysomes and markedly increased the stability of c-myc mRNA. Moreover, despite high, induced levels of mRNA, IFN inhibited the serum-stimulated rise in odc enzyme activity and the increased rate of fibronectin protein synthesis. By contrast, IFN had no effect on c-fos protein synthesis, nor did it affect the synthesis of most, but not all, proteins detectable by two-dimensional gel electrophoresis. The data suggest IFN inhibits proliferation by suppressing the expression of a subset of growth factor-inducible genes through a selective, posttranscriptional mechanism.
Levine
R A
RA
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Seshadri
T
T
Hann
S R
SR
Campisi
J
J
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D011519:Proto-Oncogenes / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism
D005353:Fibronectins; D006133:Growth Substances; D007370:Interferon Type I; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D009955:Ornithine Decarboxylase