The c-fos protein interacts with $\text{c}\text{-}\text{Jun}\text{AP}\text{-1}$ to stimulate transcription of AP-1 responsive genes

Abstract

Cell lines stably transfected with metal inducible, MT-fos chimeric genes were used to study the ability of the c-fos gene product, Fos, to act as a transcriptional trans-activator. In 3T3MTfos cells, induction of Fos expression led to specific trans-activation of an AP-1 responsive reporter gene. Induction of Fos expression in F9MTfos cells, however, did not lead to trans-activation. Since, unlike NIH3T3 cells, F9 cells do not contain detectable levels of AP-1, we examined whether a $\text{c}\text{-}\text{Jun}\text{AP}\text{-1}$ expression vector can restore the trans-activating effect of Fos in F9MTfos cells. Transfection with a functional $\text{c}\text{-}\text{Jun}\text{AP}\text{-1}$ vector restored the specific trans-activating effect of Fos on AP-1 responsive constructs. When incubated with nondenatured cell extracts, anti-cFos antisera precipitated a protein complex composed of Fos and several Fos associated proteins (FAP). One of these, FAP p39, is structurally identical to $\text{c}\text{-}\text{Jun}\text{AP}\text{-1}$. These results suggest that Fos is a trans-acting factor that is capable of stimulating gene expression not by direct binding to DNA but by interaction with the sequence-specific transcription factor AP-1. Therefore recognition of specific cis-elements by AP-1 is a prerequisite for Fos-mediated stimulation of gene expression.