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Transactivation of c-fos and β-actin genes by raf as a step in early response to transmembrane signals

Nature volume 344, pages 463–466 (1990)Cite this article

Abstract

A PRIMARY response to many growth factor-induced trans-membrane signals is the rapid activation of transcription of the proto-oncogene c-fos and other early-response genes, including the β-actin gene1,2. The c-raf gene encodes a cytoplasmic serine/threonine kinase, raf-1 (réf. 3), whose activity is also respon-sive to transmembrane signals4,5 and which in mutant form can transform cells6. Here we show that in transient assays, the v-raf protein, which is a constitutively activated oncogenic counterpart of raf-1, can transactivate transcription from two early-response promoters, including the c-fos promoter from human and murine cells and the human β-actin gene promoter. Multiple elements of the human fos promoter, including the dyad symmetry element necessary for growth-factor induction, an octanucleotide direct repeat element, and the region spanning the sequence from nucleo-tides –225 to –99 can all serve as targets for raf induction. The c-myc promoter and two adenovirus-2 early promoters are not induced. These findings indicate that raf kinase, when activated by a transmembrane signal or by mutation of a regulatory domain, can phosphorylate a factor(s) capable of regulating transcription of the c-fos and actin genes. The oncogenic form of raf may transform by constitutively activating early response proto-oncogenes such as c-fos.

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Authors and Affiliations

  1. Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, 550 First Avenue, New York, New York, 10016, USA

    Sumayah Jamal & Edward Ziff

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  1. Sumayah Jamal
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  2. Edward Ziff
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Jamal, S., Ziff, E. Transactivation of c-fos and β-actin genes by raf as a step in early response to transmembrane signals. Nature 344, 463–466 (1990). https://doi.org/10.1038/344463a0

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