An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes

Rosalynn J. Miltenberger, Janelle Cortner, Peggy J. Farnham

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The proto-oncogene Raf-1 is a cytoplasmic serine/ threonine kinase implicated in the signaling process in cell proliferation. To determine if Raf-1 is sufficient and necessary to transmit mitogenic signals to growth-responsive genes, we examined the effect of constitutively activated (v-raf) or inhibitory (Raf-C4) Raf-1 proteins on reporter gene activation in transient expression assays of NIH 3T3 cells. In serum-starved cells, v-raf strongly activated transcription from the promoters of the immediate-early genes c-fos and egr-2, as well as the proximal or B promoter of the late growth response gene rep-3 (rep-3b). Two other late response gene promoters, cad and dhfr, were only modestly activated by v-raf, however. An individual serum response element from the c-fos or egr-2 promoter conferred both serum-inducibility and v-raf-responsiveness to a heterologous promoter. Consistent with the degree to which antisense c-raf-1 RNA and dominant-negative Raf-1 proteins interfere with NIH 3T3 cell proliferation, Raf-C4 reduced serum-induced transcription from the egr-2 and rep-3b promoters in a dose-dependent manner by 50%. In contrast, Raf-C4 did not significantly reduce transcription from the c-fos or cad promoters or the serum response element-driven heterologous promoters. We conclude that Raf-1 is both sufficient and necessary to activate a subset of early and late growth response genes.

Original languageEnglish (US)
Pages (from-to)15674-15680
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number21
StatePublished - Jul 25 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Miltenberger, R. J., Cortner, J., & Farnham, P. J. (1993). An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes. Journal of Biological Chemistry, 268(21), 15674-15680.