Direct interaction between fos and jun nuclear oncoproteins: role of the 'leucine zipper' domain

Abstract

Gene expression is modulated by the specific interactions of nuclear proteins with unique regulatory sequences in the genome. Proteins involved in transcriptional regulation seem to be either transcription factors or transcription modulators and their interactions are crucial in determining whether the expression of a specific gene is activated or repressed. Recently¹, the product of the proto-oncogene jun has been identified as the transcription factor AP-1, whereas nuclear oncoproteins fos and myc have been implicated in transcriptional transregulation of several promoters^2–6. Furthermore, the products of the fos and jun proto-oncogenes are associated in some transcription complexes^3,5,7. Although the nature of the association is unclear, the two proteins co-immunoprecipitate with fos antibodies in nuclear extracts^8–10. Here, we report studies that demonstrate that the fos protein directly modulates jun function by means of a heterodimer of fos and jun proteins. The fos 'leucine zipper'¹¹ domain is necessary for the DNA binding of the heterodimer; a distinct domain, localized in the C-terminal region of the fos protein, is responsible for transcriptional regulation.