Posttranscriptional changes in growth factor-inducible gene regulation caused by antiproliferative interferons.

AUTOR(ES)

Levine, R A

RESUMO

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.

Documentos Relacionados

• Expression of cyr61, a growth factor-inducible immediate-early gene.
• An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene.
• Identification of mouse histone deacetylase 1 as a growth factor-inducible gene.
• Regulatory elements in the promoter region of vgf, a nerve growth factor-inducible gene.
• Functional serum response elements upstream of the growth factor-inducible gene zif268.